SMC protein

From Wikipedia, the free encyclopedia
Jump to: navigation, search

SMC proteins represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics.[1][2][3] SMC stands for Structural Maintenance of Chromosomes.

Classification[edit]

Eukaryotic SMCs[edit]

Eukaryotes have at least six SMC proteins in individual organisms, and they form three distinct heterodimers with specialized functions:

  • A pair of SMC1 and SMC3 constitutes the core subunits of the cohesin complexes involved in sister chromatid cohesion.[4][5][6]
  • Likewise, a pair of SMC2 and SMC4 acts as the core of the condensin complexes implicated in chromosome condensation.[7][8]
  • A dimer composed of SMC5 and SMC6 functions as part of a yet-to-be-named complex implicated in DNA repair and checkpoint responses.[9]

Each complex contains a distinct set of non-SMC regulatory subunits. Some organisms have variants of SMC proteins. For instance, mammals have a meiosis-specific variant of SMC1, known as SMC1β.[10] The nematode Caenorhabditis elegans has an SMC4-variant that has a specialized role in dosage compensation.[11]

subfamily complex S. cerevisiae S. pombe C. elegans D. melanogaster vertebrates
SMC1α cohesin Smc1 Psm1 SMC-1 DmSmc1 SMC1α
SMC2 condensin Smc2 Cut14 MIX-1 DmSmc2 CAP-E/SMC2
SMC3 cohesin Smc3 Psm3 SMC-3 DmSmc3 SMC3
SMC4 condensin Smc4 Cut3 SMC-4 DmSmc4 CAP-C/SMC4
SMC5 SMC5-6 Smc5 Smc5 C27A2.1 CG32438 SMC5
SMC6 SMC5-6 Smc6 Smc6/Rad18 C23H4.6, F54D5.14 CG5524 SMC6
SMC1β cohesin (meiotic) - - - - SMC1β
SMC4 variant dosage compensation complex - - DPY-27 - -

Prokaryotic SMCs[edit]

SMC proteins are conserved from bacteria to humans. Most bacteria have a single SMC protein in individual species that forms a homodimer.[12] In a subclass of Gram-negative bacteria including Escherichia coli, a distantly related protein known as MukB plays an equivalent role.[13]

Molecular structure[edit]

Structure of SMC dimer

Primary structure[edit]

SMC proteins are 1,000-1,500 amino-acid long. They have a modular structure that is composed of the following domains:

  1. Walker A ATP-binding motif
  2. coiled-coil region I
  3. hinge region
  4. coiled-coil region II
  5. Walker B ATP-binding motif; signature motif

Secondary and tertiary structure[edit]

SMC dimers form a V-shaped molecule with two long coiled-coil arms.[14][15] To make such a unique structure, an SMC protomer is self-folded through anti-parallel coiled-coil interactions, forming a rod-shaped molecule. At one end of the molecule, the N-terminal and C-terminal domains together form an ATP-binding domain. The other end is called a hinge domain. Two protomers then dimerize through their hinge domains and assemble a V-shaped dimer.[16][17] The length of the coiled-coil arms is ~50 nm long. Such long "antiparallel" coiled-coils are very rare, and found only among SMC proteins (and its relatives such as Rad50). The ATP-binding domain of SMC proteins is structurally related to that of ABC transporters, a large family of transmembrane proteins that actively transport small molecules across cellular membranes. It is thought that the cycle of ATP binding and hydrolysis modulates the cycle of closing and opening of the V-shaped molecule, but the detailed mechanisms of action of SMC proteins remain to be determined.

Genes[edit]

The following human genes encode SMC proteins:

See also[edit]

References[edit]

  1. ^ Losada A, Hirano T (2005). "Dynamic molecular linkers of the genome: the first decade of SMC proteins". Genes Dev 19 (11): 1269–1287. doi:10.1101/gad.1320505. PMID 15937217. 
  2. ^ Nasmyth K, Haering CH. (2005). "The structure and function of SMC and kleisin complexes.". Annu. Rev. Biochem. 74: 595–648. doi:10.1146/annurev.biochem.74.082803.133219. PMID 15952899. 
  3. ^ Huang CE, Milutinovich M, Koshland D (2005). "Rings, bracelet or snaps: fashionable alternatives for Smc complexes". Philos Trans R Soc Lond B Biol Sci 360 (1455): 537–42. doi:10.1098/rstb.2004.1609. PMC 1569475. PMID 15897179. 
  4. ^ Michaelis C, Ciosk R, Nasmyth K. (1997). "Cohesins: chromosomal proteins that prevent premature separation of sister chromatids". Cell 91 (1): 35–45. doi:10.1016/S0092-8674(01)80007-6. PMID 9335333. 
  5. ^ Guacci V, Koshland D, Strunnikov A. (1998). "A direct link between sister chromatid cohesion and chromosome condensation revealed through the analysis of MCD1 in S. cerevisiae". Cell 91 (1): 47–57. doi:10.1016/S0092-8674(01)80008-8. PMC 2670185. PMID 9335334. 
  6. ^ Losada A, Hirano M, Hirano T. (1998). "Identification of Xenopus SMC protein complexes required for sister chromatid cohesion". Genes Dev. 12 (13): 1986–1997. doi:10.1101/gad.12.13.1986. PMID 9649503. 
  7. ^ Hirano T, Kobayashi R, Hirano M. (1997). "Condensins, chromosome condensation complex containing XCAP-C, XCAP-E and a Xenopus homolog of the Drosophila Barren protein". Cell 89 (4): 511–21. doi:10.1016/S0092-8674(00)80233-0. PMID 9160743. 
  8. ^ Ono T, Losada A, Hirano M, Myers MP, Neuwald AF, Hirano T. (2003). "Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells". Cell 115 (1): 109–21. doi:10.1016/S0092-8674(03)00724-4. PMID 14532007. 
  9. ^ Fousteri MI, Lehmann AR. (2000). "A novel SMC protein complex in Schizosaccharomyces pombe contains the Rad18 DNA repair protein". EMBO J. 19 (7): 1691–1702. doi:10.1093/emboj/19.7.1691. PMID 10747036. 
  10. ^ Revenkova E, Eijpe M, Heyting C, Gross B, Jessberger R. (2001). "Novel meiosis-specific isoform of mammalian SMC1". Mol. Cell. Biol. 21 (20): 6984–6998. doi:10.1128/MCB.21.20.6984-6998.2001. PMC 99874. PMID 11564881. 
  11. ^ Chuang PT, Albertson DG, Meyer BJ. (1994). "DPY-27:a chromosome condensation protein homolog that regulates C. elegans dosage compensation through association with the X chromosome". Cell 79 (3): 459–474. doi:10.1016/0092-8674(94)90255-0. PMID 7954812. 
  12. ^ Britton RA, Lin DC, Grossman AD. (1998). "Characterization of a prokaryotic SMC protein involved in chromosome partitioning.". Genes Dev. 12 (9): 1254–1259. doi:10.1101/gad.12.9.1254. PMID 9573042. 
  13. ^ Niki H, Jaffé A, Imamura R, Ogura T, Hiraga S. (1991). "The new gene mukB codes for a 177 kd protein with coiled-coil domains involved in chromosome partitioning of E. coli.". EMBO J. 10 (1): 183–193. PMID 1989883. 
  14. ^ Melby TE, Ciampaglio CN, Briscoe G, Erickson HP. (1998). "The symmetrical structure of structural maintenance of chromosomes (SMC) and MukB proteins: long, antiparallel coiled coils, folded at a flexible hinge.". J. Cell Biol. 142 (6): 1595–1604. doi:10.1083/jcb.142.6.1595. PMID 9744887. 
  15. ^ Anderson DE, Losada A, Erickson HP, Hirano T. (2002). "Condensin and cohesin display different arm conformations with characteristic hinge angles.". J. Cell Biol. 156 (6): 419–424. doi:10.1083/jcb.200111002. PMID 11815634. 
  16. ^ Haering CH, Löwe J, Hochwagen A, Nasmyth K. (2002). "Molecular architecture of SMC proteins and the yeast cohesin complex.". Mol. Cell 9 (4): 773–788. doi:10.1016/S1097-2765(02)00515-4. PMID 11983169. 
  17. ^ Hirano M, Hirano T. (2002). "Hinge-mediated dimerization of SMC protein is essential for its dynamic interaction with DNA.". EMBO J. 21 (21): 5733–5744. doi:10.1093/emboj/cdf575. PMID 12411491.