Wikipedia

Intermediate filament

Intermediate filaments(IFs) arecytoskeletalstructural components found in the cells ofvertebrates,and manyinvertebrates.[1][2][3]Homologues of the IF protein have been noted in an invertebrate, thecephalochordateBranchiostoma.[4]

Intermediate filament tail domain
Structure of lamin a/c globular domain
Identifiers
SymbolIF_tail
PfamPF00932
InterProIPR001322
PROSITEPDOC00198
SCOP21ivt/SCOPe/SUPFAM
Available protein structures:
Pfam structures/ECOD
PDBRCSB PDB;PDBe;PDBj
PDBsumstructure summary
Intermediate filament rod domain
Human vimentin coil 2b fragment (cys2)
Identifiers
SymbolFilament
PfamPF00038
InterProIPR016044
PROSITEPDOC00198
SCOP21gk7/SCOPe/SUPFAM
Available protein structures:
Pfam structures/ECOD
PDBRCSB PDB;PDBe;PDBj
PDBsumstructure summary
Intermediate filament head (DNA binding) region
Identifiers
SymbolFilament_head
PfamPF04732
InterProIPR006821
SCOP21gk7/SCOPe/SUPFAM
Available protein structures:
Pfam structures/ECOD
PDBRCSB PDB;PDBe;PDBj
PDBsumstructure summary
Peripherin neuronal intermediate filament protein
Identifiers
SymbolPRPH
Alt. symbolsNEF4
NCBI gene5630
HGNC9461
OMIM170710
RefSeqNM_006262.3
UniProtP41219
Other data
LocusChr. 12q13.12
Search for
StructuresSwiss-model
DomainsInterPro
Nestin neuronal stem cell intermediate filament protein
Identifiers
SymbolNES
NCBI gene10763
HGNC7756
OMIM600915
RefSeqNP_006608
UniProtP48681
Other data
LocusChr. 1q23.1
Search for
StructuresSwiss-model
DomainsInterPro

Intermediate filaments are composed of a family of relatedproteinssharing common structural and sequence features. Initially designated 'intermediate' because their average diameter (10nm) is between those of narrowermicrofilaments(actin) and widermyosinfilaments found in muscle cells, the diameter of intermediate filaments is now commonly compared toactinmicrofilaments (7 nm) andmicrotubules(25 nm).[1][5]Animal intermediate filaments are subcategorized into six types based on similarities in amino acid sequence andproteinstructure.[6]Most types arecytoplasmic,but one type, Type V is anuclear lamin.Unlike microtubules, IF distribution in cells shows no good correlation with the distribution of eithermitochondriaorendoplasmic reticulum.[7]

Structure

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Structure of intermediate filament

The structure of proteins that form intermediate filaments (IF) was first predicted by computerized analysis of theamino acid sequenceof a human epidermalkeratinderived from clonedcDNAs.[8]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.[9]As suggested by the first model, all IF proteins appear to have a centralAlpha -helicalrod domain that is composed of four Alpha -helical segments (named as 1A, 1B, 2A and 2B) separated by three linker regions.[9][10]

The central building block of an intermediate filament is a pair of two intertwined proteins that is called acoiled-coil structure.This name reflects the fact that the structure of each protein is helical, and the intertwined pair is also a helical structure. Structural analysis of a pair of keratins shows that the two proteins that form the coiled-coil bind byhydrophobic interactions.[11][12]The charged residues in the central domain do not have a major role in the binding of the pair in the central domain.[11]

Cytoplasmic IFs assemble into non-polar unit-length filaments (ULFs). Identical ULFs 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.[13] 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.

TheN-terminusand theC-terminusof IF proteins are non- Alpha -helical regions and show wide variation in their lengths and sequences across IF families. The N-terminal "head domain" bindsDNA.[14]Vimentinheads are able to alternucleararchitecture andchromatindistribution, and the liberation of heads byHIV-1proteasemay play an important role in HIV-1 associated cytopathogenesis andcarcinogenesis.[15]Phosphorylationof the head region can affect filament stability.[16]The head has been shown to interact with the rod domain of the sameprotein.[17]

C-terminal "tail domain" shows extreme length variation between different IF proteins.[18]

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, unlikeactinortubulin,intermediate filaments do not contain abinding sitefor anucleoside triphosphate.

Cytoplasmic IFs do not undergotreadmillinglike microtubules and actin fibers, but are dynamic.[19]

Biomechanical properties

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IFs are rather deformable proteins that can be stretched several times their initial length.[20]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.[12]Initially the coupled Alpha -helices of unit-length filaments uncoil as they're strained, then as the strain increases they transition intobeta-sheets,and finally at increased strain the hydrogen bonds between beta-sheets slip and the ULF monomers slide along each other.[12]

Types

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There are about 70 different human 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.

Animal IFs are subcategorized into six types based on similarities in amino acid sequence andproteinstructure:[6]

Types I and II – acidic and basic keratins

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Keratinintermediate filaments (stained red) aroundepithelial cells
Further information:Cytokeratin

These proteins are the most diverse among IFs and constitutetype I (acidic)andtype II (basic)IF proteins. The manyisoformsare 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.[6]

Cytokeratinfilaments laterally associate with each other to create a thick bundle of ~50 nm radius. The optimal radius of such bundles is determined by the interplay between the long range electrostatic repulsion and short range hydrophobic attraction.[21]Subsequently, these bundles would intersect through junctions to form a dynamic network, spanning the cytoplasm of epithelial cells.

Type III

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Vimentinfibers infibroblasts

There are four proteins classed as type III intermediate filament proteins, which may formhomo-orheteropolymericproteins.

Type IV

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Type V – nuclear lamins

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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,lamin B1andB2,are expressed from the LMNB1 and LMNB2 genes on 5q23 and 19q13, respectively. A-type lamins are only expressed followinggastrulation.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 thenuclear envelopeand throughout the nucleoplasm in thenucleoplasmic 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.[6]

Type VI

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  • Beaded filaments:Filensin,Phakinin.[6]
  • Nestin(was once proposed for reclassification but due to differences, remains as a type VI IF protein)[24]

Vertebrate-only. Related to type I-IV. Used to contain other newly discovered IF proteins not yet assigned to a type.[25]

Function

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Cell adhesion

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At theplasma membrane,some keratins or desmin interact withdesmosomes(cell-cell adhesion) andhemidesmosomes(cell-matrix adhesion) via adapter proteins.

Associated proteins

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Filaggrinbinds to keratin fibers in epidermal cells.Plectinlinks vimentin to other vimentin fibers, as well as to microfilaments, microtubules, andmyosinII. Kinesin is being researched and is suggested to connect vimentin to tubulin via motor proteins.

Keratin filaments in epithelial cells link todesmosomes(desmosomes connect the cytoskeleton together) throughplakoglobin,desmoplakin,desmogleins,anddesmocollins;desminfilaments are connected in a similar way in heart muscle cells.

Diseases arising from mutations in IF genes

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In other organisms

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IF proteins are universal among animals in the form of a nuclear lamin. The Hydra has an additional "nematocilin" derived from the lamin. Cytoplasmic IFs (type I-IV) are only found inBilateria;they also arose from agene duplicationevent involving "type V" nuclear lamin. In addition, a few other diverse types of eukaryotes have lamins, suggesting an early origin of the protein.[25]

There was not really a concrete definition of an "intermediate filament protein", in the sense that the size or shape-based definition does not cover amonophyletic group.With the inclusion of unusual proteins like the network-forming beaded lamins (type VI), the current classification is moving to a clade containing nuclear lamin and its many descendants, characterized by sequence similarity as well as the exon structure. Functionally-similar proteins out of this clade, likecrescentins,alveolins, tetrins, and epiplasmins, are therefore only "IF-like". They likely arose throughconvergent evolution.[25]

References

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  1. ^abHerrmann H, Bär H, Kreplak L, Strelkov SV, Aebi U (July 2007). "Intermediate filaments: from cell architecture to nanomechanics".Nature Reviews. Molecular Cell Biology.8(7): 562–73.doi:10.1038/nrm2197.PMID17551517.S2CID27115011.
  2. ^Chang L, Goldman RD (August 2004). "Intermediate filaments mediate cytoskeletal crosstalk".Nature Reviews. Molecular Cell Biology.5(8): 601–13.doi:10.1038/nrm1438.PMID15366704.S2CID31835055.
  3. ^Traub, P. (2012),Intermediate Filaments: A Review,Springer Berlin Heidelberg, p. 33,ISBN978-3-642-70230-3
  4. ^Karabinos A, Riemer D, Erber A, Weber K (October 1998)."Homologues of vertebrate type I, II and III intermediate filament (IF) proteins in an invertebrate: the IF multigene family of the cephalochordate Branchiostoma".FEBS Letters.437(1–2): 15–8.doi:10.1016/S0014-5793(98)01190-9.PMID9804163.S2CID7886395.
  5. ^Ishikawa H, Bischoff R, Holtzer H (September 1968)."Mitosis and intermediate-sized filaments in developing skeletal muscle".The Journal of Cell Biology.38(3): 538–55.doi:10.1083/jcb.38.3.538.PMC2108373.PMID5664223.
  6. ^abcdefSzeverenyi I, Cassidy AJ, Chung CW, Lee BT, Common JE, Ogg SC, et al. (March 2008)."The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases".Human Mutation.29(3): 351–360.doi:10.1002/humu.20652.PMID18033728.S2CID20760837.
  7. ^Soltys BJ, Gupta RS (1992). "Interrelationships of endoplasmic reticulum, mitochondria, intermediate filaments, and microtubules--a quadruple fluorescence labeling study".Biochemistry and Cell Biology.70(10–11): 1174–86.doi:10.1139/o92-163.PMID1363623.
  8. ^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.PMID6186381.S2CID35796315.
  9. ^abHanukoglu 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.PMID6191871.S2CID21490380.
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  11. ^abHanukoglu I, Ezra L (Jan 2014)."Proteopedia entry: coiled-coil structure of keratins".Biochemistry and Molecular Biology Education.42(1): 93–4.doi:10.1002/bmb.20746.PMID24265184.S2CID30720797.
  12. ^abcQin Z, Kreplak L, Buehler MJ (October 2009)."Hierarchical structure controls nanomechanical properties of vimentin intermediate filaments".PLOS ONE.4(10): e7294.Bibcode:2009PLoSO...4.7294Q.doi:10.1371/journal.pone.0007294.PMC2752800.PMID19806221.
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  14. ^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.PMID11513613.
  15. ^Shoeman RL, Hüttermann 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".Molecular Biology of the Cell.12(1): 143–54.doi:10.1091/mbc.12.1.143.PMC30574.PMID11160829.
  16. ^Takemura M, Gomi H, Colucci-Guyon E, Itohara S (August 2002)."Protective role of phosphorylation in turnover of glial fibrillary acidic protein in mice".The Journal of Neuroscience.22(16): 6972–9.doi:10.1523/JNEUROSCI.22-16-06972.2002.PMC6757867.PMID12177195.
  17. ^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".Journal of Structural Biology.137(1–2): 97–108.doi:10.1006/jsbi.2002.4437.PMID12064937.
  18. ^Quinlan R, Hutchison C, Lane B (1995). "Intermediate filament proteins".Protein Profile.2(8): 795–952.PMID8771189.
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  20. ^Herrmann H, Bär H, Kreplak L, Strelkov SV, Aebi U (July 2007). "Intermediate filaments: from cell architecture to nanomechanics".Nature Reviews. Molecular Cell Biology.8(7): 562–73.doi:10.1038/nrm2197.PMID17551517.S2CID27115011.Qin Z, Kreplak L, Buehler MJ (October 2009)."Hierarchical structure controls nanomechanical properties of vimentin intermediate filaments".PLOS ONE.4(10): e7294.Bibcode:2009PLoSO...4.7294Q.doi:10.1371/journal.pone.0007294.PMC2752800.PMID19806221.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.PMID17187357.S2CID6560740.Qin Z, Buehler MJ, Kreplak L (January 2010). "A multi-scale approach to understand the mechanobiology of intermediate filaments".Journal of Biomechanics.43(1): 15–22.doi:10.1016/j.jbiomech.2009.09.004.PMID19811783.Qin Z, Kreplak L, Buehler MJ (October 2009). "Nanomechanical properties of vimentin intermediate filament dimers".Nanotechnology.20(42): 425101.Bibcode:2009Nanot..20P5101Q.doi:10.1088/0957-4484/20/42/425101.PMID19779230.S2CID6870454.
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Further reading

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