Editing Keratin (section)

== Protein structure ==
The first sequences of keratins were determined by [[Israel Hanukoglu]] and [[Elaine Fuchs]] (1982, 1983).<ref name="Hanukoglu_1982">{{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 = 243–252 | date = November 1982 | pmid = 6186381 | doi = 10.1016/0092-8674(82)90424-x }}</ref><ref name="Hanukoglu_1983">{{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 = 915–924 | date = July 1983 | pmid = 6191871 | doi = 10.1016/0092-8674(83)90034-x }}</ref> These sequences revealed that there are two distinct but homologous keratin families, which were named type I and type II keratins.<ref name="Hanukoglu_1983" /> By analysis of the primary structures of these keratins and other intermediate filament proteins, Hanukoglu and Fuchs suggested a model in which keratins and intermediate filament proteins contain a central ~310 residue domain with four segments in α-helical conformation that are separated by three short linker segments predicted to be in beta-turn conformation.<ref name="Hanukoglu_1983" /> This model has been confirmed by the determination of the crystal structure of a helical domain of keratins.<ref name="Lee_2012">{{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 = 707–715 | date = July 2012 | pmid = 22705788 | pmc = 3864793 | doi = 10.1038/nsmb.2330 }}</ref>

=== Type I and II keratins ===
The human genome has 54 functional annotated keratin genes, of which 28 are [[type I keratin]]s and 26 are [[type II keratin]]s.<ref>{{cite book | vauthors = Bernot KM, Coulombe PA, Zaher H | chapter = Cytoskeleton &#124; Intermediate Filaments | title = Encyclopedia of Biological Chemistry III | pages = 193–199 | date = 2021 | doi = 10.1016/B978-0-12-819460-7.00037-2 | quote = Type I and type II IFs are part of the keratin (or cytokeratin) family of proteins found in all epithelia. The human genome features 54 functional keratin genes, with 28 type I and 26 type II keratin genes (see Table 1). Type I keratins tend to be smaller and acidic compared to the larger, neutral–basic type II keratins. | isbn = 978-0-12-822040-5 }}</ref> 
[[File:Keratin.jpg|thumb|Keratin (high molecular weight) in [[bile duct]] cell and oval cells of [[horse]] [[liver]].]]

Fibrous keratin molecules supercoil to form a very stable, left-handed [[superhelix|superhelical]] motif to multimerise, forming filaments consisting of multiple copies of the keratin [[monomer]].<ref name="Voet_1998">{{Cite book | vauthors = Voet D, Voet JG, Pratt CW | chapter = Proteins: Three-Dimensional Structure | title = Fundamentals of Biochemistry | pages = 158 | date = 1998 | quote = Fibrous proteins are characterized by a single type of secondary structure: a keratin is a left-handed coil of two a helices | chapter-url = http://biochem118.stanford.edu/Papers/Protein%20Papers/Voet%26Voet%20chapter6.pdf | archive-url = https://web.archive.org/web/20060917080333/http://biochem118.stanford.edu/Papers/Protein%20Papers/Voet%26Voet%20chapter6.pdf | archive-date = 2006-09-17 | url-status = live | publisher = Wiley | isbn = 978-0-471-58650-0 }}</ref>

The major force that keeps the coiled-coil structure is [[Hydrophobicity|hydrophobic interactions]] between [[apolar]] residues along the keratin's helical segments.<ref name="Hanukoglu_2014">{{cite journal | vauthors = Hanukoglu I, Ezra L | title = Proteopedia entry: Coiled-coil structure of keratins: Multimedia in Biochemistry and Molecular Biology Education | journal = Biochemistry and Molecular Biology Education : a Bimonthly Publication of the International Union of Biochemistry and Molecular Biology | volume = 42 | issue = 1 | pages = 93–94 | date = January 2014 | pmid = 24265184 | doi = 10.1002/bmb.20746 | doi-access = free }}</ref>

Limited interior space is the reason why the [[triple helix]] of the (unrelated) structural protein [[collagen]], found in [[skin]], [[cartilage]] and [[bone]], likewise has a high percentage of [[glycine]]. The connective tissue protein [[elastin]] also has a high percentage of both glycine and [[alanine]]. [[Silk]] [[fibroin]], considered a β-keratin, can have these two as 75–80% of the total, with 10–15% [[serine]], with the rest having bulky side groups. The chains are antiparallel, with an alternating C → N orientation.<ref>{{cite web | title = Secondary Protein | url = http://elmhurst.edu/~chm/vchembook/566secprotein.html | publisher = Elmhurst.edu | access-date = 2010-09-23 | url-status = dead | archive-url = https://web.archive.org/web/20100922111144/http://elmhurst.edu/~chm/vchembook/566secprotein.html | archive-date = 2010-09-22 }}</ref> A preponderance of [[amino acid]]s with small, [[chemical reaction|nonreactive]] side groups is characteristic of structural proteins, for which H-bonded close packing is more important than [[chemical specificity]].

===Disulfide bridges===
In addition to intra- and intermolecular [[hydrogen bond]]s, the distinguishing feature of keratins is the presence of large amounts of the [[sulfur]]-containing amino acid [[cysteine]], required for the [[disulfide bond|disulfide bridges]] that confer additional strength and rigidity by permanent, thermally stable [[cross-link|crosslinking]]<ref>{{cite web | title = What is Keratin? | url = http://www.wisegeek.org/what-is-keratin.htm | publisher = WiseGEEK | access-date = 11 May 2014 | archive-date = 13 May 2014 | archive-url = https://web.archive.org/web/20140513010609/http://www.wisegeek.org/what-is-keratin.htm | url-status = live }}</ref>—in much the same way that non-protein sulfur bridges stabilize [[vulcanization|vulcanized]] [[rubber]]. Human hair is approximately 14% cysteine. The [[pungency|pungent]] smells of burning hair and skin are due to the volatile sulfur compounds formed. Extensive disulfide bonding contributes to the [[soluble|insolubility]] of keratins, except in a small number of solvents such as [[dissociation (chemistry)|dissociating]] or [[redox|reducing]] agents.
[[File:Toe nail.jpg|thumb|A human [[Nail (anatomy)|toenail]] that fell off after a small trauma.]]
The more flexible and elastic keratins of hair have fewer interchain disulfide bridges than the keratins in [[mammalian]] [[fingernail]]s, hooves and claws (homologous structures), which are harder and more like their analogs in other vertebrate classes.<ref>{{cite journal | vauthors = H Bragulla H, G Homberger D | title = Structure and functions of keratin proteins in simple, stratified, keratinized and cornified epithelia | journal = Journal of Anatomy | volume = 214 | issue = 4 | pages = 516–559 | date = Apr 2009 | pmid = 19422428 | pmc = 2736122 | doi = 10.1111/j.1469-7580.2009.01066.x }}</ref> Hair and other α-keratins consist of [[alpha helix|α-helically]] coiled single protein strands (with regular intra-chain [[hydrogen bond|H-bonding]]), which are then further twisted into superhelical [[rope]]s that may be further coiled. The β-keratins of reptiles and birds have β-pleated sheets twisted together, then stabilized and hardened by disulfide bridges.

Thiolated polymers ([[thiomers]]) can form disulfide bridges with cysteine substructures of keratins getting covalently attached to these proteins.<ref>{{cite journal | vauthors = Leichner C, Jelkmann M, Bernkop-Schnürch A | title = Thiolated polymers: Bioinspired polymers utilizing one of the most important bridging structures in nature | journal = Advanced Drug Delivery Reviews | volume = 151-152 | pages = 191–221 | date = 2019 | pmid = 31028759 | doi = 10.1016/j.addr.2019.04.007 }}</ref> Thiomers therefore exhibit high binding properties to keratins found in hair,<ref>{{cite patent | title = Cosmetic compositions containing thiomers for hair color retention | number = 20110229430A1 | inventor = Hawkins G, Afriat IR, Xavier JH, Popescu LC | country = US | pubdate = 22 September 2011 }}</ref> on skin<ref>{{cite journal | vauthors = Grießinger J, Bonengel S, Partenhauser A, Ijaz M, Bernkop-Schnürch A | title = Thiolated polymers: Evaluation of their potential as dermoadhesive excipients | journal = Drug Development and Industrial Pharmacy | volume = 43 | issue = 2 | pages = 204–212 | date = 2017 | pmid = 27585266 | doi = 10.1080/03639045.2016.1231809 }}</ref><ref>{{cite journal | vauthors = Partenhauser A, Zupančič O, Rohrer J, Bonengel S, Bernkop-Schnürch A | title = Thiolated silicone oils as adhesive skin protectants for improved barrier function | journal = International Journal of Cosmetic Science | volume = 38 | issue = 3 | pages = 257–265 | date = 2015 | pmid = 26444859 | doi = 10.1111/ics.12284 }}</ref> and on the surface of many cell types.<ref>{{cite journal | vauthors = Le-Vinh B, Steinbring C, Nguyen Le N, Matuszczak B, Bernkop-Schnürch A | title = S-Protected thiolated chitosan versus thiolated chitosan as cell adhesive biomaterials for tissue engineering. | journal = ACS Applied Materials & Interfaces | volume = 15 | issue = 34 | pages = 40304–40316 | date = 2023 | pmid = 37594415 | pmc = 10472333 | doi = 10.1021/acsami.3c09337 }}</ref>

===Filament formation===
It has been proposed that keratins can be divided into 'hard' and 'soft' forms, or '[[cytokeratin]]s' and 'other keratins'.{{Clarify|date=May 2010}}{{dubious|reason=Not supported by source. Every keratin is cytokeratin until it gets squeezed out by cell death, which happens a bit more often for hair/nail (hard) stuff. The ref does not recommend the cyto- name at all.|date=October 2022}} That model is now understood to be correct. A new nuclear addition in 2006 to describe keratins takes this into account.<ref name="Schweizer_2006" />

Keratin filaments are [[intermediate filament]]s. Like all intermediate filaments, keratin proteins form filamentous polymers in a series of assembly steps beginning with dimerization; dimers assemble into tetramers and octamers and eventually, if the current hypothesis holds, into unit-length-filaments (ULF) capable of [[annealing (biology)|annealing]] end-to-end into long filaments.

===Pairing===

{| class="wikitable" style="margin:1em auto 1em auto"
! '''A''' (neutral-basic)
! '''B''' (acidic)
!Occurrence
|-
| [[keratin 1]], [[keratin 2]]
| [[keratin 9]], [[keratin 10]]
| [[stratum corneum]], [[keratinocyte]]s
|-
| [[keratin 3]]
| [[keratin 12]]
| [[cornea]]
|-
| [[keratin 4]]
| [[keratin 13]]
| [[stratified squamous epithelium|stratified epithelium]]
|-
| [[keratin 5]]
| [[keratin 14]], [[keratin 15]]
| stratified epithelium
|-
| [[keratin 6]]
| [[keratin 16]], [[keratin 17]]
| [[squamous epithelium]]
|-
| [[keratin 7]]
| [[keratin 19]]
| ductal epithelia
|-
| [[keratin 8]]
| [[keratin 18]], [[keratin 20]]
| simple epithelium
|}