Intermediate filament

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Structure of intermediate filament
Intermediate filament tail domain
PDB 1ifr EBI.jpg
structure of lamin a/c globular domain
Identifiers
Symbol IF_tail
Pfam PF00932
InterPro IPR001322
PROSITE PDOC00198
SCOP 1ivt
SUPERFAMILY 1ivt
Intermediate filament protein
PDB 1gk4 EBI.jpg
human vimentin coil 2b fragment (cys2)
Identifiers
Symbol Filament
Pfam PF00038
InterPro IPR016044
PROSITE PDOC00198
SCOP 1gk7
SUPERFAMILY 1gk7
Intermediate filament head (DNA binding) region
Identifiers
Symbol Filament_head
Pfam PF04732
InterPro IPR006821
SCOP 1gk7
SUPERFAMILY 1gk7

Intermediate filaments (IFs) are cytoskeletal components found in metazoan cells. They are composed of a family of related proteins sharing common structural and sequence features. Intermediate filaments have an average diameter of 10 nanometers, which is between that of 7 nm actin (microfilaments), and that of 25 nm microtubules, although they were initially designated 'intermediate' because their average diameter is between those of narrower microfilaments (actin) and wider myosin filaments found in muscle cells.[1][2] Most types of intermediate filaments are cytoplasmic, but one type, the lamins, are nuclear.

Structure[edit]

The structure of proteins that form IF was first predicted by computerized analysis of the amino acid sequence of a human epidermal keratin derived from cloned cDNAs.[3] Analysis of a second keratin sequence revealed that the two types of keratins share only about 30% amino acid sequence homology but share similar patterns of secondary structure domains.[4] As suggested by the first model, all IF proteins appear to have a central alpha-helical rod domain that is composed of four alpha-helical segments (named as 1A, 1B, 2A and 2B) separated by three linker regions. [4][5]

The N and C-termini of IF proteins are non-alpha-helical regions and show wide variation in their lengths and sequences across IF families. The basic building-block for IFs is a parallel and in-register dimer. The dimer is formed through the interaction of the rod domain to form a coiled coil.[6] Cytoplasmic IF assemble into non-polar unit-length filaments (ULF). Identical ULF associate laterally into staggered, antiparallel, soluble tetramers, which associate head-to-tail into protofilaments that pair up laterally into protofibrils, four of which wind together into an intermediate filament.[7]

Part of the assembly process includes a compaction step, in which ULF tighten and assume a smaller diameter. The reasons for this compaction are not well understood, and IF are routinely observed to have diameters ranging between 6 and 12 nm.

The N-terminal "head domain" binds DNA.[8] Vimentin heads are able to alter nuclear architecture and chromatin distribution, and the liberation of heads by HIV-1 protease may play an important role in HIV-1 associated cytopathogenesis and carcinogenesis.[9] Phosphorylation of the head region can affect filament stability.[10] The head has been shown to interact with the rod domain of the same protein.[11]

C-terminal "tail domain" shows extreme length variation between different IF proteins.[12]

The anti-parallel orientation of tetramers means that, unlike microtubules and microfilaments, which have a plus end and a minus end, IFs lack polarity and cannot serve as basis for cell motility and intracellular transport.

Also, as opposed to actin or tubulin, intermediate filaments do not contain a binding site for a nucleoside triphosphate.

Cytoplasmic IF do not undergo treadmilling like microtubules and actin fibers, but they are dynamic. For a review see: [1].

Biomechanical properties[edit]

IFs are rather deformable proteins that can be stretched several times their initial length.[13] The key to facilitate this large deformation is due to their hierarchical structure, which facilitates a cascaded activation of deformation mechanisms at different levels of strain.[6] Initially the coupled alpha-helices of unit-length filaments uncoil as they're strained, then as the strain increases they transition into beta-sheets, and finally at increased strain the hydrogen bonds between beta-sheets slip and the ULF monomers slide along each other.[6]

Types[edit]

There are about 70 different genes coding for various intermediate filament proteins. However, different kinds of IFs share basic characteristics: In general, they are all polymers that measure between 9-11 nm in diameter when fully assembled.

IF are subcategorized into six types based on similarities in amino acid sequence and protein structure.

Types I and II - Acidic and Basic Keratins[edit]

keratin intermediate filaments (stained red)

These proteins are the most diverse among IFs and constitute type I (acidic) and type II (basic) IF proteins. The many isoforms are divided in two groups:

Regardless of the group, keratins are either acidic or basic. Acidic and basic keratins bind each other to form acidic-basic heterodimers and these heterodimers then associate to make a keratin filament.

Type III[edit]

There are four proteins classed as type III IF proteins, which may form homo- or heteropolymeric proteins.

Type IV[edit]

Type V - nuclear lamins[edit]

Lamins are fibrous proteins having structural function in the cell nucleus.

In metazoan cells, there are A and B type lamins, which differ in their length and pI. Human cells have three differentially regulated genes. B-type lamins are present in every cell. B type lamins, B1 and B2, are expressed from the LMNB1 and LMNB2 genes on 5q23 and 19q13, respectively. A-type lamins are only expressed following gastrulation. Lamin A and C are the most common A-type lamins and are splice variants of the LMNA gene found at 1q21.

These proteins localize to two regions of the nuclear compartment, the nuclear lamina—a proteinaceous structure layer subjacent to the inner surface of the nuclear envelope and throughout the nucleoplasm in the nucleoplasmic "veil".

Comparison of the lamins to vertebrate cytoskeletal IFs shows that lamins have an extra 42 residues (six heptads) within coil 1b. The c-terminal tail domain contains a nuclear localization signal (NLS), an Ig-fold-like domain, and in most cases a carboxy-terminal CaaX box that is isoprenylated and carboxymethylated (lamin C does not have a CAAX box). Lamin A is further processed to remove the last 15 amino acids and its farnesylated cysteine.

During mitosis, lamins are phosphorylated by MPF, which drives the disassembly of the lamina and the nuclear envelope.

Type VI[edit]

Unclassified[edit]

Beaded Filaments-- Filensin, Phakinin

Cell adhesion[edit]

At the plasma membrane, some keratins interact with desmosomes (cell-cell adhesion) and hemidesmosomes (cell-matrix adhesion) via adapter proteins.

Associated proteins[edit]

Filaggrin binds to keratin fibers in epidermal cells. Plectin links vimentin to other vimentin fibers, as well as to microfilaments, microtubules, and myosin II. Kinesin is being researched and is suggested to connect vimentin to tubulin via motor proteins.

Keratin filaments in epithelial cells link to desmosomes (desmosomes connect the cytoskeleton together) through plakoglobin, desmoplakin, desmogleins, and desmocollins; desmin filaments are connected in a similar way in heart muscle cells.

Diseases arising from mutations in IF genes[edit]

References[edit]

  1. ^ Ishikawa H, Bischoff R, Holtzer H (September 1968). "Mitosis and intermediate-sized filaments in developing skeletal muscle". J. Cell Biol. 38 (3): 538–55. doi:10.1083/jcb.38.3.538. PMC 2108373. PMID 5664223. 
  2. ^ Herrmann H, Bär H, Kreplak L, Strelkov SV, Aebi U (July 2007). "Intermediate filaments: from cell architecture to nanomechanics". Nat. Rev. Mol. Cell Biol. 8 (7): 562–73. doi:10.1038/nrm2197. PMID 17551517. 
  3. ^ Hanukoglu I, Fuchs E (November 1982). "The cDNA sequence of a human epidermal keratin: divergence of sequence but conservation of structure among intermediate filament proteins". Cell 31 (1): 243–52. doi:10.1016/0092-8674(82)90424-X. PMID 6186381. 
  4. ^ a b Hanukoglu I, Fuchs E (July 1983). "The cDNA sequence of a Type II cytoskeletal keratin reveals constant and variable structural domains among keratins". Cell 33 (3): 915–24. doi:10.1016/0092-8674(83)90034-X. PMID 6191871. 
  5. ^ Lee CH, Kim MS, Chung BM, Leahy DJ, Coulombe PA (July 2012). "Structural basis for heteromeric assembly and perinuclear organization of keratin filaments". Nat. Struct. Mol. Biol. 19 (7): 707–15. doi:10.1038/nsmb.2330. PMID 22705788. 
  6. ^ a b c Qin Z, Kreplak L, Buehler MJ (2009). "Hierarchical structure controls nanomechanical properties of vimentin intermediate filaments". PLoS ONE 4 (10): e7294. doi:10.1371/journal.pone.0007294. PMC 2752800. PMID 19806221. 
  7. ^ Lodish H; Berk A, Zipursky SL, et al. (2000). Molecular Cell Biology. New York: W. H. Freeman. p. Section 19.6, Intermediate Filaments. ISBN 0-07-243940-8. 
  8. ^ Wang Q, Tolstonog GV, Shoeman R, Traub P (August 2001). "Sites of nucleic acid binding in type I-IV intermediate filament subunit proteins". Biochemistry 40 (34): 10342–9. doi:10.1021/bi0108305. PMID 11513613. 
  9. ^ Shoeman RL, Huttermann C, Hartig R, Traub P (January 2001). "Amino-terminal polypeptides of vimentin are responsible for the changes in nuclear architecture associated with human immunodeficiency virus type 1 protease activity in tissue culture cells". Mol. Biol. Cell 12 (1): 143–54. PMC 30574. PMID 11160829. 
  10. ^ Takemura M, Gomi H, Colucci-Guyon E, Itohara S (August 2002). "Protective role of phosphorylation in turnover of glial fibrillary acidic protein in mice". J. Neurosci. 22 (16): 6972–9. PMID 12177195. 
  11. ^ Parry DA, Marekov LN, Steinert PM, Smith TA (2002). "A role for the 1A and L1 rod domain segments in head domain organization and function of intermediate filaments: structural analysis of trichocyte keratin". J. Struct. Biol. 137 (1-2): 97–108. doi:10.1006/jsbi.2002.4437. PMID 12064937. 
  12. ^ Quinlan R, Hutchison C, Lane B (1995). "Intermediate filament proteins". Protein Profile 2 (8): 795–952. PMID 8771189. 
  13. ^ Herrmann H, Bär H, Kreplak L, Strelkov SV, Aebi U (July 2007). "Intermediate filaments: from cell architecture to nanomechanics". Nat. Rev. Mol. Cell Biol. 8 (7): 562–73. doi:10.1038/nrm2197. PMID 17551517. Qin Z, Kreplak L, Buehler MJ (2009). "Hierarchical structure controls nanomechanical properties of vimentin intermediate filaments". PLoS ONE 4 (10): e7294. doi:10.1371/journal.pone.0007294. PMC 2752800. PMID 19806221. Kreplak L, Fudge D (January 2007). "Biomechanical properties of intermediate filaments: from tissues to single filaments and back". BioEssays 29 (1): 26–35. doi:10.1002/bies.20514. PMID 17187357. Qin Z, Buehler MJ, Kreplak L (January 2010). "A multi-scale approach to understand the mechanobiology of intermediate filaments". J Biomech 43 (1): 15–22. doi:10.1016/j.jbiomech.2009.09.004. PMID 19811783. Qin Z, Kreplak L, Buehler MJ (October 2009). "Nanomechanical properties of vimentin intermediate filament dimers". Nanotechnology 20 (42): 425101. doi:10.1088/0957-4484/20/42/425101. PMID 19779230. 
  14. ^ Steinert PM, Chou YH, Prahlad V, Parry DA, Marekov LN, Wu KC, Jang SI, Goldman RD (April 1999). "A high molecular weight intermediate filament-associated protein in BHK-21 cells is nestin, a type VI intermediate filament protein. Limited co-assembly in vitro to form heteropolymers with type III vimentin and type IV alpha-internexin". J. Biol. Chem. 274 (14): 9881–90. doi:10.1074/jbc.274.14.9881. PMID 10092680. 
  15. ^ Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Zu Knyphausen E, Vorgerd M, Gummert J, Milting H (December 2010). "De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy". Hum. Mol. Genet. 19 (23): 4595–607. doi:10.1093/hmg/ddq387. PMID 20829228. 
  16. ^ Brodehl A, Hedde PN, Dieding M, Fatima A, Walhorn V, Gayda S, Šarić T, Klauke B, Gummert J, Anselmetti D, Heilemann M, Nienhaus GU, Milting H (May 2012). "Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants". J. Biol. Chem. 287 (19): 16047–57. doi:10.1074/jbc.M111.313841. PMC 3346104. PMID 22403400. 

Further reading[edit]

External links[edit]

This article incorporates text from the public domain Pfam and InterPro IPR001322

This article incorporates text from the public domain Pfam and InterPro IPR006821