Editing Intermediate filament (section)

== Structure ==
[[File:Intermediate filament.svg|thumb|right|300px|Structure of intermediate filament]]
The structure of proteins that form intermediate filaments (IF) was first predicted by computerized analysis of the [[amino acid sequence]] of a human epidermal [[keratin]] derived from cloned [[complementary DNA|cDNAs]].<ref name="pmid6186381">{{cite journal | vauthors = Hanukoglu I, Fuchs E | title = The cDNA sequence of a human epidermal keratin: divergence of sequence but conservation of structure among intermediate filament proteins | journal = Cell | volume = 31 | issue = 1 | pages = 243–52 | date = November 1982 | pmid = 6186381 | doi = 10.1016/0092-8674(82)90424-X | url = https://zenodo.org/record/890743 | s2cid = 35796315 }}</ref> 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.<ref name="pmid6191871">{{cite journal | vauthors = Hanukoglu I, Fuchs E | title = The cDNA sequence of a Type II cytoskeletal keratin reveals constant and variable structural domains among keratins | journal = Cell | volume = 33 | issue = 3 | pages = 915–24 | date = July 1983 | pmid = 6191871 | doi = 10.1016/0092-8674(83)90034-X | url = https://zenodo.org/record/890739 | s2cid = 21490380 }}</ref> 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.<ref name="pmid6191871" /><ref name="pmid22705788">{{cite journal | vauthors = Lee CH, Kim MS, Chung BM, Leahy DJ, Coulombe PA | title = Structural basis for heteromeric assembly and perinuclear organization of keratin filaments | journal = Nature Structural & Molecular Biology | volume = 19 | issue = 7 | pages = 707–15 | date = June 2012 | pmid = 22705788 | pmc = 3864793 | doi = 10.1038/nsmb.2330 }}</ref>

The central building block of an intermediate filament is a pair of two intertwined proteins that is called a [[coiled-coil|coiled-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 by [[hydrophobic interactions]].<ref name="2014-Hanukoglu">{{cite journal | vauthors = Hanukoglu I, Ezra L | title = Proteopedia entry: coiled-coil structure of keratins | journal = Biochemistry and Molecular Biology Education | volume = 42 | issue = 1 | pages = 93–4 | date = Jan 2014 | pmid = 24265184 | doi = 10.1002/bmb.20746 | s2cid = 30720797 | doi-access = free }}</ref><ref name="Qin2009">{{cite journal | vauthors = Qin Z, Kreplak L, Buehler MJ | title = Hierarchical structure controls nanomechanical properties of vimentin intermediate filaments | journal = PLOS ONE | volume = 4 | issue = 10 | pages = e7294 | date = October 2009 | pmid = 19806221 | pmc = 2752800 | doi = 10.1371/journal.pone.0007294 | bibcode = 2009PLoSO...4.7294Q | doi-access = free }}</ref> The charged residues in the central domain do not have a major role in the binding of the pair in the central domain.<ref name="2014-Hanukoglu" />

Cytoplasmic IFs assemble into non-polar unit-length filaments (ULFs). Identical ULFs associate laterally into staggered, [[Antiparallel (biochemistry)|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.<ref>{{Cite book | vauthors=Lodish H, Berk A, Zipursky SL | url=https://archive.org/details/isbn_9780072930283/page/ | title=Molecular Cell Biology | year=2000 | publisher=W. H. Freeman | location=New York | isbn=978-0-07-243940-3 | page=[https://archive.org/details/isbn_9780072930283/page/ Section 19.6, Intermediate Filaments] | display-authors=etal | url-access=registration }}</ref>
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&nbsp;nm.{{cn|date=April 2025}}

The [[N-terminus]] and the [[C-terminus]] of IF proteins are non-alpha-helical regions and show wide variation in their lengths and sequences across IF families.
The N-terminal "head domain" binds [[DNA]].<ref name="pmid11513613">{{cite journal | vauthors = Wang Q, Tolstonog GV, Shoeman R, Traub P | title = Sites of nucleic acid binding in type I-IV intermediate filament subunit proteins | journal = Biochemistry | volume = 40 | issue = 34 | pages = 10342–9 | date = August 2001 | pmid = 11513613 | doi = 10.1021/bi0108305 }}</ref> [[Vimentin]] heads are able to alter [[cell nucleus|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]].<ref name="pmid11160829">{{cite journal | vauthors = Shoeman RL, Hüttermann C, Hartig R, Traub P | title = 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 | journal = Molecular Biology of the Cell | volume = 12 | issue = 1 | pages = 143–54 | date = January 2001 | pmid = 11160829 | pmc = 30574 | doi = 10.1091/mbc.12.1.143 }}</ref> [[Phosphorylation]] of the head region can affect filament stability.<ref name="pmid12177195">{{cite journal | vauthors = Takemura M, Gomi H, Colucci-Guyon E, Itohara S | title = Protective role of phosphorylation in turnover of glial fibrillary acidic protein in mice | journal = The Journal of Neuroscience | volume = 22 | issue = 16 | pages = 6972–9 | date = August 2002 | pmid = 12177195 | pmc = 6757867 | doi = 10.1523/JNEUROSCI.22-16-06972.2002 }}</ref> The head has been shown to interact with the rod domain of the same [[protein]].<ref name="pmid12064937">{{cite journal | vauthors = Parry DA, Marekov LN, Steinert PM, Smith TA | title = 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 = Journal of Structural Biology | volume = 137 | issue = 1–2 | pages = 97–108 | year = 2002 | pmid = 12064937 | doi = 10.1006/jsbi.2002.4437 }}</ref>

C-terminal "tail domain" shows extreme length variation between different IF proteins.<ref name="pmid8771189">{{cite journal | vauthors = Quinlan R, Hutchison C, Lane B | title = Intermediate filament proteins | journal = Protein Profile | volume = 2 | issue = 8 | pages = 795–952 | year = 1995 | pmid = 8771189 }}</ref>

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.{{cn|date=April 2025}}

Also, unlike [[actin]] or [[tubulin]], intermediate filaments do not contain a [[binding site]] for a [[nucleoside triphosphate]].

Cytoplasmic IFs do not undergo [[treadmilling]] like microtubules and actin fibers, but are dynamic.<ref name="Helfand">{{cite journal | vauthors = Helfand BT, Chang L, Goldman RD | title = Intermediate filaments are dynamic and motile elements of cellular architecture | journal = Journal of Cell Science | volume = 117 | issue = Pt 2 | pages = 133–41 | date = January 2004 | pmid = 14676269 | doi = 10.1242/jcs.00936 | doi-access = free }}</ref>