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Rendering of a crystal structure.
Eukaryotic ribosome. The 40S subunit is on the left, the 60S subunit on the right. The ribosomal RNA (rRNA) core is represented as a grey tube, expansion segments are shown in red. Universally conserved proteins are shown in blue. These proteins have homologs in eukaryotes, archaea and bacteria. Proteins shared only between eukaryotes and archaea are shown in orange, and proteins specific to eukaryotes are shown in red. PDB identifiers 4a17, 4A19, 2XZM aligned to 3U5B, 3U5C, 3U5D, 3U5E

Overview[edit]

The Ribosome is a large and complex molecular machine that catalyzes the synthesis of proteins, referred to as translation. Herein, the ribosome selects aminoacylated transfer RNAs (tRNAs) based on the sequence of a protein encoding messenger RNA (mRNA) and covalently links the amino acids into a polypeptide chain. Ribosomes from all organisms share a highly conserved catalytic center. However, the ribosomes of eukaryotes (animals, plants, fungi and many unicellular organisms with a nucleus) are much larger than prokaryotic (bacterial and archaeal) ribosomes and subject to more complex regulation and biogenesis pathways. These Eukaryotic ribosomes are also known as 80S ribosomes, referring to their sedimentation coefficients in Svedberg units, because they sediment faster than the prokaryotic (70S) ribosomes. Eukaryotic ribosomes have two unequal subunits, designated small subunit (40S) and large subunit (60S) according to their sedimentation coefficients. Both subunits contain dozens of ribosomal proteins arranged on a scaffold composed of ribosomal RNA (rRNA). The small subunit monitors the complementarity between tRNA anticodon and mRNA, while the large subunit catalyzes peptide bond formation.

Composition[edit]

Compared to their prokaryotic homologs, many of the eukaryotic ribosomal proteins are enlarged by insertions or extensions to the converved core. Furthermore, several additional proteins are found in the small and large subunits of eukaryotic ribosomes, which do not have prokaryotic homologs. The 40S subunit contains a 18S ribosomal RNA (abbreviated 18S rRNA), which is homologous to the prokaryotic 16S rRNA. The 60S subunit contains a 26S rRNA that is homologous to the prokaryotic 23S ribosomal RNA. In addition, it contains a 5.8S rRNA that corresponds to the 5'end of the 23S rRNA, and a short 5S rRNA. Both 18S and 26S have multiple insertions to the core rRNA fold of their prokaryotic counterparts, which are called expansion segments. For a detailed list of proteins, including archaeal and bacterial homologs please refer to the separate articles on the 40S and 60S subunits.

Eukaryotic[1] Bacterial[1]
Ribosome Sedimentation coefficient 80 S 70 S
Molecular mass ~3.2*106 Da ~2.0*106 Da
Diameter ~250-300 Å ~200 Å
Large subunit Sedimentation coefficient 60 S 50 S
Molecular mass ~2.0*106 Da ~1.3*106 Da
Proteins 47 33
rRNAs
Small subunit Sedimentation coefficient 40 S 30 S
Molecular mass ~1.2*106 Da ~0.7*106 Da
Proteins 32 20
rRNAs

Structure Determination[edit]

After the determination of the first bacterial [2][3][4] and archaeal [5] ribosome structures in the 1990s it took another decade until atomic structures of the eukaryotic ribosome were obtained by X-Ray crystallography, mainly because of the difficulties in obtaining crystals of sufficient quality.[6][7][8] In 2010, the atomic structure of the 40S subunit from Tetrahymena thermophila, a ciliate, was reported.[6] The structure was determined in complex with initiation factor 1 (eIF1) and therefore not only revealed the fold of the entire 18S ribosomal RNA and of all ribosomal proteins of the 40S subunit, but also defined the interactions with eIF1. In 2011, the structure of the 60S subunit from the same organism was solved in complex with initiation factor 6 (eIF6),[7] and was followed immediately by the structure of the entire 80S ribosome [8] from the yeast Saccharomyces cerevisiae. Atomic coordinates (PDB files) and structure factors of the eukaryotic ribosome have been deposited in the Protein Data Bank (PDB) under the following accession codes:

Complex Source Organism Resolution PDB Identifier[9]
40S:eIF1 T. thermophila 3.9 Å
60S:eIF6 T. thermophila 3.5 Å
80S:Stm1 S. cerevisiae 3.0 Å

Architecture of the Eukaryotic Ribosome[edit]

General Architectural Features[edit]

Some general architectural features of the ribosome are conserved across kingdoms:[10] The shape of the small subunit can be subdivided into two large segments, the head and the body. Characteristic features of the body include the left and right feet, the shoulder and the platform. The head features a pointed protrusion reminiscent of a bird's beak. In the characteristic "crown view" of the large subunit, structural landmarks include the central protuberance, the L1-stalk and the P-stalk.[11][12] The majority of the eukaryote-specific RNA and protein elements are found on the solvent-exposed sides of the 40S [6] and 60S[7] subunits. The subunit interface, as well as important functional regions such as the peptidyl transferase center and the decoding site are mostly conserved, with some differences observed in the surrounding regions. In stark contrast to prokaryotic ribosomal proteins, which interact primarily with RNA, the eukaryote-specific protein segments engage in a multitude of protein-protein interactions. Long-distance interactions are mediated by eukaryote-specific helical extensions of ribosomal proteins, and several eukaryotic ribosomal proteins jointly to form inter-protein beta-sheets.

Crystal Structures of the Eukaryotic Ribosomal Subunits from T. thermophila
  • 40S subunit viewed from the subunit interface side, PDB identifier 2XZM
    40S subunit viewed from the subunit interface side, PDB identifier 2XZM
  • 40S subunit viewed from the solvent-exposed side, PDB identifier 2XZM
    40S subunit viewed from the solvent-exposed side, PDB identifier 2XZM
  • 60S subunit viewed from the subunit interface side, PDB identifiers 4A17, 4A19
    60S subunit viewed from the subunit interface side, PDB identifiers 4A17, 4A19
  • rendering of crystal structure
    60S subunit viewed from the solvent-exposed side, PDB identifiers 4A17, 4A19

The ribosomal RNA core is represented as a grey tube, expansion segments are shown in red. Universally conserved proteins are shown in blue. These proteins have homologs in eukaryotes, archaea and bacteria. Proteins Shared only between eukaryotes and archaea are shown in orange, and proteins specific to eukaryotes are shown in red.

Co-evolution of rRNA and Proteins[edit]

The structure of the 40S subunit revealed that the eukaryote-specific proteins (rpS7, rpS10, rpS12 and RACK1), as well as numerous eukaryote-specific extensions of proteins, are located on the solvent-exposed side of the small subunit.[6] Here, they participate in the stabilization of rRNA expansion segments. Moreover, the beak of the 40S subunit is remodeled, as rRNA has been replaced by proteins rpS10 and rpS12.[6] As observed for the 40S subunit, all eukaryote-specific proteins of the 60S subunit (RPL6, RPL22, RPL27, RPL28, RPL29 and RPL36) and many extensions are located at the solvent-exposed side, forming an intricate network of interactions with eukaryotic-specific RNA expansion segments. RPL6, RPL27 and RPL29 mediate contacts between the ES sets ES7–ES39, ES31–ES20–ES26 and ES9–ES12, respectively and RPL28 stabilized expansion segment ES7A.[7]

Ubiquitin Fusion Proteins[edit]

In eukaryotes, the small subunit protein rpS27A(S31) and the large subunit protein RPL40 are processed polypeptides, which are translated as fusion proteins carrying N-terminal Ubiquitin domains. Both proteins are located next to important functional centers of the ribosome: The uncleaved ubiquitin domains of rpS27A(S31) and RPL40 would be positioned in the decoding site and near the translation factor binding site, respectively. These positions suggest that proteolytic cleavage is an essential step in the production of functional ribosomes.[6][7] Indeed, mutations of the linker between the core of rpS27A(S31) and the ubiquitin domain are lethal in yeast.[13]

Active Site Region[edit]

Comparisons between bacterial, archaeal and eukaryotic ribosome structures reveal a very high degree of conservation in the active site (PTC) region. None of the eukaryote-specific protein elements is close enough to directly participate in catalysis.[7] However, RPL29 projects to within 18Å of the active site in T. thermophila, and eukaryote-specific extensions interlink several proteins in the vicinity of the PTC of the 60S subunit,[7][11] while the corresponding 50S proteins are singular entities.[5]

Intersubunit Bridges[edit]

Contacts across the two ribosomal subunits are known as intersubunit bridges. In the eukaryotic ribosome, additional contacts are made by 60S expansion segments and proteins.[8] Specifically, the C-terminal extension of the 60S protein RPL19 interacts with ES6E of the 40S rRNA, and the C-terminal extension of the 60S protein RPL24 interacts with 40S rpS6 and rRNA helix h10. Moreover, the 60S expansion segments ES31 and ES41 interact with rpS3A(S1) and rpS8 of the 40S subunit, respectively, and the basic 25-amino-acid peptide RPL41 is positioned at the subunit interface in the 80S ribosome, interacting with rRNA elements of both subunits.[8][11]

Ribosomal Proteins with Roles in Signaling[edit]

Two 40S ribosomal proteins (RACK1 and rpS6) have been implicated in signaling: RACK1, the Receptor of Activated Protein Kinase C (PKC), is an integral component of the eukaryotic ribosome and is located at the back of the head, in proximity of rpS17.[6] It links signal-transduction pathways directly to the ribosome (reviewed in [14]). Ribosomal protein rpS6 is located at the right foot of the 40S subunit [6] and is phosphorylated in response to mammalian target of rapamycin (mTOR) signaling.[15]

Functional Aspects[edit]

Translation Initiation[edit]

Protein synthesis is primarily regulated at the stage of translation initiation. In eukaryotes, the canonical initiation pathway requires at least 12 protein initiation factors, some of which are themselves large complexes.[16] The structures of the 40S:eIF1 [6] and 60S:eIF6 [7] complexes provide first detailed insights into the atomic interactions between the eukaryotic ribosome and regulatory factors. eIF1 is involved in start codon selection, and eIF6 sterically precludes the joining of subunits. However, structural information on the eukaryotic initiaion factors and their interactions with the ribosome is limited, and largely derived from homology models or low-resolution analyses.[17] Elucidation of the interactions between the eukaryotic ribosome and initiation factors at an atomic level is essential for a mechanistic understanding of the regulatory processes, but represents a significant technical challenge, because of the inherent dynamics and flexibility of the initiation complexes.

Regulatory Roles of Ribosomal Proteins[edit]

Recent evidence suggests that individual proteins of the eukaryotic ribosome may directly contribute to the regulation of translation.[18] Specifically, mutations in RPL38 lead to developmental abnormalities, but not to global translational alterations [19] Moreover, the specific defects [20] and the increased cancer susceptibility [21] that result from mutations in ribosomal proteins may support such a regulatory role.

Protein Translocation and Targeting[edit]

To exert their functions in the cell newly synthesized proteins must be targeted to the appropriate location in the cell, which is achieved protein targeting and translocation systems.[22] The growing polypeptide leaves the ribosome through a narrow tunnel in the large subunit. The region around the exit tunnel of the 60S subunit is very similar to the bacterial and archaeal 50S subunits. Additional elements are restricted to the second tier of proteins around the tunnel exit, possibly by conserved interactions with components of the translocation machinery.[7] The targeting and translocation machinery is much more complex in eukaryotes.[23]

Ribosomal Diseases and Cancer[edit]

Ribosomopathies are congenital human disorders resulting from defects in ribosomal protein or rRNA genes, or other genes whose products are implicated in ribosome biogenesis.[24] Examples include X-linked Dyskeratosis congenita (X-DC),[21] Diamond–Blackfan anemia,[20] Treacher-Collins-Syndrome (TCS) [25][20] and Shwachman–Bodian–Diamond syndrome (SBDS).[24] SBDS is caused by mutations in the SBDS protein that affects its ability to couple GTP hydrolysis by the GTPase EFL1 to the release of eIF6 from the 60S subunit.[26]

Therapeutic Opportunities[edit]

The ribosome is a prominent drug target and many antibacterials interfere with translation at different stages of the elongation cycle [27] Most clinically relevant translation compounds are inhibitors of bacterial translation, but inhibitors of eukaryotic translation may also hold therapeutic potential for application in cancer or antifungal chemotherapy.[28] Elongation inhibitors show antitumor activity 'in vivo' and 'in vitro'.[29][30][31] One inhibitor of eukaryotic translation elongation is the glutarimide antibiotic cycloheximide (CHX), which was co-crystallized with the eukaryotic 60S subunit [7] and binds in the in the ribosomal E-­site. The structural characterization of the eukaryotic ribosome [6][8][7] enables the use of structure based methods for the design of novel therapeutics, and allows the structural differences to the bacterial ribosome to be exploited, improving the selectivity and drug and therefore reducing adverse effects.

References[edit]

  1. ^ a b Values are based on the ribosomes of T. thermophila (PDB:4A17,4A19) and Thermus thermophilus (PDB 2WDL, 2WDK). The exact size, weight and number of proteins varies from organism to organism.
  2. ^ Clemons WM Jr, May JL, Wimberly BT, McCutcheon JP, Capel MS, Ramakrishnan V. Structure of a bacterial 30S ribosomal subunit at 5.5 A resolution. Nature. 1999 Aug 26;400(6747):833-40. PMID 10476960.
  3. ^ Cate JH, Yusupov MM, Yusupova GZ, Earnest TN, Noller HF. X-ray crystal structures of 70S ribosome functional complexes. Science. 1999 Sep 24;285(5436):2095-104. PMID 10497122.
  4. ^ Yusupov MM, Yusupova GZ, Baucom A, Lieberman K, Earnest TN, Cate JH, Noller HF. Crystal structure of the ribosome at 5.5 A resolution. Science. 2001 May 4;292(5518):883-96. Epub 2001 Mar 29. PMID 11283358.
  5. ^ a b Ban N, Nissen P, Hansen J, Moore PB, Steitz TA. The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. Science. 2000 Aug 11;289(5481):905-20. PMID 10937989.
  6. ^ a b c d e f g h i j Rabl J, Leibundgut M, Ataide SF, Haag A, Ban N. Crystal structure of the eukaryotic 40S ribosomal subunit in complex with initiation factor 1. Science. 2011 Feb 11;331(6018):730-6. doi: 10.1126/science.1198308. Epub 2010 Dec 23. PMID 21205638.
  7. ^ a b c d e f g h i j k Klinge S, Voigts-Hoffmann F, Leibundgut M, Arpagaus S, Ban N. Crystal structure of the eukaryotic 60S ribosomal subunit in complex with initiation factor 6. Science. 2011 Nov 18;334(6058):941-8. doi: 10.1126/science.1211204. Epub 2011 Nov 3. PMID 22052974.
  8. ^ a b c d e Ben-Shem A, Garreau de Loubresse N, Melnikov S, Jenner L, Yusupova G, Yusupov M. The structure of the eukaryotic ribosome at 3.0 Å resolution. Science. 2011 Dec 16;334(6062):1524-9. doi: 10.1126/science.1212642. Epub 2011 Nov 17. PMID 22096102.
  9. ^ Due to size limitations, ribosome structures are often split into several coordinate files
  10. ^ Melnikov S, Ben-Shem A, Garreau de Loubresse N, Jenner L, Yusupova G, Yusupov M. One core, two shells: bacterial and eukaryotic ribosomes. Nat Struct Mol Biol. 2012 Jun 5;19(6):560-7. doi: 10.1038/nsmb.2313. Review. PMID 22664983.
  11. ^ a b c Klinge S, Voigts-Hoffmann F, Leibundgut M, Ban N. Atomic structures of the eukaryotic ribosome. Trends Biochem Sci. 2012 May;37(5):189-98. doi:10.1016/j.tibs.2012.02.007. Epub 2012 Mar 20. Review. PMID 22436288.
  12. ^ Jenner L, Melnikov S, de Loubresse NG, Ben-Shem A, Iskakova M, Urzhumtsev A, Meskauskas A, Dinman J, Yusupova G, Yusupov M. Crystal structure of the 80S yeast ribosome. Curr Opin Struct Biol. 2012 Dec;22(6):759-67. doi: 10.1016/j.sbi.2012.07.013. Epub 2012 Aug 8. PMID 22884264.
  13. ^ Lacombe T, García-Gómez JJ, de la Cruz J, Roser D, Hurt E, Linder P, Kressler D. Linear ubiquitin fusion to Rps31 and its subsequent cleavage are required for the efficient production and functional integrity of 40S ribosomal subunits. Mol Microbiol. 2009 Apr;72(1):69-84. doi: 10.1111/j.1365-2958.2009.06622.x. Epub 2009 Feb 4. PMID 19210616.
  14. ^ Regulation of eukaryotic translation by the RACK1 protein: a platform for signalling molecules on the ribosome. Nilsson J, Sengupta J, Frank J, Nissen P. EMBO Rep. 2004 Dec;5(12):1137-41. Review.
  15. ^ Palm L, Andersen J, Rahbek-Nielsen H, Hansen TS, Kristiansen K, Højrup P. The phosphorylated ribosomal protein S7 in Tetrahymena is homologous with mammalian S4 and the phosphorylated residues are located in the C-terminal region. Structural characterization of proteins separated by two-dimensional polyacrylamide gel electrophoresis. J Biol Chem. 1995 Mar 17;270(11):6000-5. PMID 7890730.
  16. ^ Hinnebusch AG, Lorsch JR. The mechanism of eukaryotic translation initiation: new insights and challenges. Cold Spring Harb Perspect Biol. 2012 Oct 1;4(10).doi:pii: a011544. 10.1101/cshperspect.a011544. Review. PMID 22815232.
  17. ^ Voigts-Hoffmann F, Klinge S, Ban N. Structural insights into eukaryotic ribosomes and the initiation of translation. Curr Opin Struct Biol. 2012 Dec;22(6):768-77. doi: 10.1016/j.sbi.2012.07.010. Epub 2012 Aug 10. PMID 22889726.
  18. ^ Topisirovic I, Sonenberg N. Translational control by the eukaryotic ribosome. Cell. 2011 Apr 29;145(3):333-4. doi: 10.1016/j.cell.2011.04.006. PMID 21529706
  19. ^ Kondrashov N, Pusic A, Stumpf CR, Shimizu K, Hsieh AC, Xue S, Ishijima J, Shiroishi T, Barna M. Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning. Cell. 2011 Apr 29;145(3):383-97. doi:10.1016/j.cell.2011.03.028. PMID 21529712.
  20. ^ a b c Narla A, Ebert BL. Translational medicine: ribosomopathies. Blood. 2011 Oct 20;118(16):4300-1. doi: 10.1182/blood-2011-08-372250
  21. ^ a b Stumpf CR, Ruggero D. The cancerous translation apparatus. Curr Opin Genet Dev. 2011 Aug;21(4):474-83. doi: 10.1016/j.gde.2011.03.007. Epub 2011 May 3. Review. PMID 21543223; PMC 3481834.
  22. ^ Boehringer, Daniel, Greber, Basil, Ban, Nenad. Mechanistic insight into co-translational protein processing, folding, targeting, and membrane insertion. Ribosomes, 405-418. 2011, http://dx.doi.org/10.1007/978-3-7091-0215-2_32
  23. ^ Markus T. Bohnsack, Enrico Schleiff, The evolution of protein targeting and translocation systems, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1803, Issue 10, October 2010, Pages 1115-1130, ISSN 0167-4889, 10.1016/j.bbamcr.2010.06.005.
  24. ^ a b Narla A, Ebert BL. Ribosomopathies: human disorders of ribosome dysfunction. Blood. 2010 Apr 22;115(16):3196-205. doi: 10.1182/blood-2009-10-178129. Epub 2010 Mar 1. Review. PMID 20194897; PMC 2858486.
  25. ^ Dauwerse JG, Dixon J, Seland S, Ruivenkamp CA, van Haeringen A, Hoefsloot LH, Peters DJ, Boers AC, Daumer-Haas C, Maiwald R, Zweier C, Kerr B, Cobo AM, Toral JF, Hoogeboom AJ, Lohmann DR, Hehr U, Dixon MJ, Breuning MH, Wieczorek D. Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. Nat Genet. 2011 Jan;43(1):20-2. doi: 10.1038/ng.724. Epub 2010 Dec 5. PMID 21131976.
  26. ^ Finch AJ, Hilcenko C, Basse N, Drynan LF, Goyenechea B, Menne TF, González Fernández A, Simpson P, D'Santos CS, Arends MJ, Donadieu J, Bellanné-Chantelot C, Costanzo M, Boone C, McKenzie AN, Freund SM, Warren AJ. Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome. Genes Dev. 2011 May 1;25(9):917-29. doi: 10.1101/gad.623011. PMID 21536732; PMC 3084026.
  27. ^ Blanchard SC, Cooperman BS, Wilson DN. Probing translation with small-molecule inhibitors. Chem Biol. 2010 Jun 25;17(6):633-45. doi:10.1016/j.chembiol.2010.06.003. Review. PMID 20609413; PMC 2914516.
  28. ^ Pelletier,J. & Peltz,S.W.,2007.Therapeutic Opportunities in Translation. Cold Spring Harbor Monograph Archive, 48(0), pp.855–895.
  29. ^ Schneider-­‐Poetsch, T., Usui, T., et al., 2010a. Garbled messages and corrupted translations. Nature Methods, 6(3), pp.189–198.
  30. ^ Schneider-­‐Poetsch, T., Ju, J., et al., 2010b. Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin. Nat Chem Biol, 6(3), pp.209–217.
  31. ^ Dang, Y. et al., 2011. Inhibition of eukaryotic translation elongation by the antitumor natural product Mycalamide B. RNA (New York, N.Y.), 17(8), pp.1578–1588.

40S[edit]

Ribosomal particles are denoted according to their sedimentation coefficients in Svedberg units. The 40S subunit is the small subunit of eukaryotic 80S ribosomes. It is structurally and functionally related to the 30S subunit of 70S prokaryotic ribosomes.[1][2][3][4] However, the 40S subunit is much larger than the prokaryotic 30S subunit and contains many additional protein segments, as well as rRNA expansion segments. More information can be found in the article on the eukaryotic ribosome.

Overall Structure[edit]

The shape of the small subunit can be subdivided into two large segments, the head and the body. Characteristic features of the body include the left and right feet, the shoulder and the platform. The head features a pointed protrusion reminiscent of a bird's beak. The mRNA binds in the cleft between the head and the body, and there are three binding sites for tRNA, the A-site, P-site and E-site (see article on protein translation for details). The core of the 40S subunit is formed by the 18S ribosomal RNA (abbreviated 18S rRNA), which is homologous to the prokaryotic 16S rRNA. This rRNA core is decorated with dozens of proteins. In the figure "Crystal Structure of the Eukaryotic 40S Ribosomal Subunit from T. thermophila", the ribosomal RNA core is represented as a grey tube and expansion segments are shown in red. Proteins which have homologs in eukaryotes, archaea and bacteria are shown as blue ribbons. Proteins shared only between eukaryotes and archaea are shown as orange ribbons and proteins specific to eukaryotes are shown as red ribbons.

Crystal Structure of the Eukaryotic 40S Ribosomal Subunit from T. thermophila
  • 40S subunit viewed from the subunit interface side, PDB identifier 2XZM
    40S subunit viewed from the subunit interface side, PDB identifier 2XZM
  • rendering of crystal structure
    40S subunit viewed from the solvent-exposed side, PDB identifier 2XZM

40S Ribosomal Proteins[edit]

The table "40S ribosomal proteins" shows the individual protein folds of the 40S subunit colored by conservation as above. The eukaryote-specific extensions, ranging from a few residues or loops to very long alpha helices and additional domains, are highlighted in red.[1] For a details, refer to the article on the eukaryotic ribosome. Historically, different nomenclatures have been used for ribosomal proteins. For instance, proteins have been numbered according to their migration properties in gel electrophoresis experiments. Therefore, different names may refer to homologous proteins from different organism, while identical names not necessarily denote homologous proteins. The table "40S ribosomal proteins" crossreferences the human ribosomal protein names with yeast, bacterial and archaeal homologs.[5] Further information can be found in the ribosomal protein gene database (RPG).[5]

40S ribosomal proteins
Structure (Eukaryotic) [6] H. sapiens[7][5] Conservation[8] S. cerevisiae[9] Bacterial homolog (E. coli) Archaeal homolog
RPSA EAB S0 S2p S2
RPS2 EAB S2 S5p S5p
RPS3 EAB S3 S3p S3p
RPS3A EA S1 n/a S3Ae
RPS4 EA S4 n/a S4e
RPS5 EAB S5 S7p S5p
RPS6 EA S6 n/a S6e
RPS7 E S7 n/a n/a
RPS8 EA S8 n/a S8e
RPS9 EAB S9 S4p S4p
RPS10 E S10 n/a n/a
RPS11 EAB S11 S17p S17p
RPS12 E S12 n/a n/a
RPS13 EAB S13 S15p S15p
RPS14 EAB S14 S11p S11p
RPS15 EAB S15 S19p S19p
RPS15A EAB S22 S8p S8p
RPS16 EAB S16 S9p S9p
RPS17 EA S17 n/a S17e
RPS18 EAB S18 S13p S13p
RPS19 EA S19 n/a S19e
RPS20 EAB S20 S10p S10p
RPS21 E S21 n/a n/a
RPS23 EAB S23 S12p S12p
RPS24 EA S24 n/a S24e
RPS25 EA S25 n/a S25e
RPS26 EA S26 n/a S26e
RPS27 EA S27 n/a S27e
RPS27A EA S31 n/a S27ae
RPS28 EA S28 n/a S28e
RPS29 EAB S29 S14p S14p
RPS30 EA S30 n/a S30e
RACK1 E Asc1 n/a n/a

External links[edit]

References[edit]

  1. ^ a b Rabl J, Leibundgut M, Ataide SF, Haag A, Ban N. Crystal structure of the eukaryotic 40S ribosomal subunit in complex with initiation factor 1. Science. 2011 Feb 11;331(6018):730-6. doi: 10.1126/science.1198308. Epub 2010 Dec 23. PMID 21205638.
  2. ^ Ben-Shem A, Garreau de Loubresse N, Melnikov S, Jenner L, Yusupova G, Yusupov M. The structure of the eukaryotic ribosome at 3.0 Å resolution. Science. 2011 Dec 16;334(6062):1524-9. doi: 10.1126/science.1212642. Epub 2011 Nov 17. PMID 22096102.
  3. ^ Wimberly BT, Brodersen DE, Clemons WM Jr, Morgan-Warren RJ, Carter AP, Vonrhein C, Hartsch T, Ramakrishnan V. Structure of the 30S ribosomal subunit. Nature. 2000 Sep 21;407(6802):327-39. PMID 11014182.
  4. ^ Schmeing TM, Ramakrishnan V. What recent ribosome structures have revealed about the mechanism of translation. Nature. 2009 Oct 29;461(7268):1234-42. doi:10.1038/nature08403. Epub 2009 Oct 18. Review. PMID 19838167.
  5. ^ a b c Nakao A, Yoshihama M, Kenmochi N. RPG: the Ribosomal Protein Gene database. Nucleic Acids Res. 2004 Jan 1;32(Database issue):D168-70. PMID 14681386; PMC 308739.
  6. ^ Structure of the T. thermophila,' proteins from the structures of the large subunit PDBS 417, 4A19 and small subunit PDB 2XZM
  7. ^ Nomenclature according to the ribosomal protein gene database, applies to H. sapiens and T. thermophila
  8. ^ EAB means conserved in eukaryotes, archaea and bacteria, EA means conserved in eukaryotes and archaea and E means eukaryote-specific protein
  9. ^ Traditionally, ribosomal proteins were named according to their apparent molecular weight in gel electrophoresis, leading to different names for homologous proteins from different organisms. The RPG offers a unified nomenclature for ribosomal protein genes based on homology.

60S[edit]

Ribosomal particles are denoted according to their sedimentation coefficients in Svedberg units. The 60S subunit is the large subunit of eukaryotic 80S ribosomes. It is structurally and functionally related to the 50S subunit of 70S prokaryotic ribosomes.[1][2][3][4][5] However, the 60S subunit is much larger than the prokaryotic 50S subunit and contains many additional protein segments, as well as rRNA expansion segments. More information on the structure can be found in the article on the eukaryotic ribosome.

Overall Structure[edit]

Characteristic features of the large subunit, shown in the "Crown View" (as seen below) include the central protuberance (CP) and the two stalks, which are named according to their bacterial protein components (L1 stalk on the left as seen from the subunit interface and L7/L12 on the right). There are three binding sites for tRNA, the A-site, P-site and E-site (see article on protein translation for details. The core of the 60S subunit is formed by the 26S ribosomal RNA (abbreviated 26S rRNA), which is homologous to the prokaryotic 16S rRNA, which also contributes the active site (peptidyl transferase center, PTC) of the ribosome.[1][3] The rRNA core is decorated with dozens of proteins. In the figure "Crystal Structure of the Eukaryotic 60S Ribosomal Subunit from T. thermophila", the ribosomal RNA core is represented as a grey tube and expansion segments are shown in red. Proteins which have homologs in eukaryotes, archaea and bacteria are shown as blue ribbons. Proteins shared only between eukaryotes and archaea are shown as orange ribbons and proteins specific to eukaryotes are shown as red ribbons.

Crystal Structure of the Eukaryotic 60S Ribosomal Subunit from T. thermophila
  • 60S subunit viewed from the subunit interface side, PDB identifiers 4A17, 4A19
    60S subunit viewed from the subunit interface side, PDB identifiers 4A17, 4A19
  • rendering of crystal structure
    60S subunit viewed from the solvent-exposed side, PDB identifiers 4A17, 4A19

60S Ribosomal Proteins[edit]

The table "60S ribosomal proteins" shows the individual protein folds of the 60S subunit colored by conservation as above. The eukaryote-specific extensions, ranging from a few residues or loops to very long alpha helices and additional domains, are highlighted in red.[1] For a details, refer to the article on the eukaryotic ribosome. Historically, different nomenclatures have been used for ribosomal proteins. For instance, proteins have been numbered according to their migration properties in gel electrophoresis experiments. Therefore, different names may refer to homologous proteins from different organism, while identical names not necessarily denote homologous proteins. The table "60S ribosomal proteins" crossreferences the human ribosomal protein names with yeast, bacterial and archaeal homologs.[6] Further information can be found in the ribosomal protein gene database (RPG).[6]

60S ribosomal proteins
Structure (Eukaryotic) [7] H. sapiens[8][6] Conservation[9] S. cerevisiae[10] Bacterial homolog (E. coli) Archaeal homolog
RPLP0 EAB P0 L10 L10
RPL3 EAB L3 L3 L3
RPL4 EAB L4 L4 L4
RPL5 EAB L5 L18 L18p
RPL6 E L6 n/a n/a
RPL7 EAB L7 L30 L30
RPL7A EA L8 n/a L7Ae
RPL8 EAB L2 L2 L2
RPL9 EAB L9 L6 L6
RPL10 EAB L10 L16 L10e
RPL11 EAB L11 L5 L5
RPL13 EA L13 n/a L13e
RPL13A EAB L16 L13 L13
RPL14 EA L14 n/a L14e
RPL15 EA L15 n/a L15e
RPL17 EAB L17 L22 L22
RPL18 EA L18 n/a L18e
RPL18A EA L20 n/a Lx
RPL19 EA L19 n/a L19
RPL21 EA L21 n/a L21e
RPL22 E L22 n/a n/a
RPL23 EAB L23 L14 L14p
RPL23A EAB L25 L23 L23
RPL24 EA L24 n/a L24e
RPL26 EAB L26 L24 L24
RPL27 E L27 n/a n/a
RPL27A EAB L28 L15 L15
RPL28 E n/a [11][1][2] n/a n/a
RPL29 E L29 n/a n/a
RPL30 EA L30 n/a L30e
RPL31 EA L31 n/a L31e
RPL32 EA L32 n/a L32e
RPL34 EA L34 n/a L34e
RPL35 EAB L35 L29 L29
RPL35A EA L33 n/a L35Ae
RPL36 E L36 n/a n/a
RPL36A EA L42 n/a L44e
RPL37 EA L37 n/a L37e
RPL37A EA L43 n/a L37Ae
RPL38 EA L38 n/a L38e
RPL39 EA L39 n/a L37Ae
RPL40 EA L40 n/a L40e

External links[edit]

References[edit]

  1. ^ a b c d Klinge S, Voigts-Hoffmann F, Leibundgut M, Arpagaus S, Ban N. Crystal structure of the eukaryotic 60S ribosomal subunit in complex with initiation factor 6. Science. 2011 Nov 18;334(6058):941-8. doi: 10.1126/science.1211204. Epub 2011 Nov 3. PMID 22052974.
  2. ^ a b Ben-Shem A, Garreau de Loubresse N, Melnikov S, Jenner L, Yusupova G, Yusupov M. The structure of the eukaryotic ribosome at 3.0 Å resolution. Science. 2011 Dec 16;334(6062):1524-9. doi: 10.1126/science.1212642. Epub 2011 Nov 17. PMID 22096102.
  3. ^ a b Ban N, Nissen P, Hansen J, Moore PB, Steitz TA. The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. Science. 2000 Aug 11;289(5481):905-20. PMID 10937989.
  4. ^ Cate JH, Yusupov MM, Yusupova GZ, Earnest TN, Noller HF. X-ray crystal structures of 70S ribosome functional complexes. Science. 1999 Sep 24;285(5436):2095-104. PMID 10497122.
  5. ^ Yusupov MM, Yusupova GZ, Baucom A, Lieberman K, Earnest TN, Cate JH, Noller HF. Crystal structure of the ribosome at 5.5 A resolution. Science. 2001 May 4;292(5518):883-96. Epub 2001 Mar 29. PMID 11283358.
  6. ^ a b c Nakao A, Yoshihama M, Kenmochi N. RPG: the Ribosomal Protein Gene database. Nucleic Acids Res. 2004 Jan 1;32(Database issue):D168-70. PMID 14681386; PMC 308739.
  7. ^ Structure of the T. thermophila,' proteins from the structures of the large subunit PDBS 417, 4A19
  8. ^ Cite error: The named reference ReferenceA was invoked but never defined (see the help page).
  9. ^ Cite error: The named reference ReferenceB was invoked but never defined (see the help page).
  10. ^ Cite error: The named reference ReferenceC was invoked but never defined (see the help page).
  11. ^ RPL28 has no detectable homolog in yeast
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