Alpha-keratin

File:Keratin creation red.svg File:Disulfide bonds.svgα-keratin is a polypeptide chain, typically high in alanine, leucine, arginine, and cysteine, that forms a right-handed α-helix.{{Cite journal|last1=Burkhard|first1=Peter|last2=Stetefeld|first2=Jörg|last3=Strelkov|first3=Sergei V|title=Coiled coils: a highly versatile protein folding motif|journal=Trends in Cell Biology|volume=11|issue=2|pages=82–88|doi=10.1016/s0962-8924(00)01898-5|year=2001|pmid=11166216}}{{Cite journal|last1=Pace|first1=C N|last2=Scholtz|first2=J M|date=1998-07-01|title=A helix propensity scale based on experimental studies of peptides and proteins.|journal=Biophysical Journal|volume=75|issue=1|pages=422–427|issn=0006-3495|pmc=1299714|pmid=9649402|doi=10.1016/S0006-3495(98)77529-0|bibcode=1998BpJ....75..422N }} Two of these polypeptide chains twist together to form a left-handed helical structure known as a coiled coil. These coiled coil dimers, approximately 45 nm long, are bonded together with disulfide bonds, utilizing the many cysteine amino acids found in α-keratins. The dimers then align, their termini bonding with the termini of other dimers, and two of these new chains bond length-wise, all through disulfide bonds, to form a protofilament.{{Cite journal|last1=Steinert|first1=Peter M.|last2=Steven|first2=Alasdair C.|last3=Roop|first3=Dennis R.|title=The molecular biology of intermediate filaments|journal=Cell|volume=42|issue=2|pages=411–419|doi=10.1016/0092-8674(85)90098-4|pmid=2411418|year=1985|s2cid=8922569 }} Two protofilaments aggregate to form a protofibril, and four protofibrils polymerize to form the intermediate filament (IF). The IF is the basic subunit of α-keratins. These IFs are able to condense into a super-coil formation of about 7 nm in diameter, and can be type I, acidic, or type II, basic. The IFs are finally embedded in a keratin matrix that either is high in cysteine or glycine, tyrosine, and phenylalanine residues. The different types, alignments, and matrices of these IFs account for the large variation in α-keratin structures found in mammals.{{Cite journal|last1=McKittrick|first1=J.|last2=Chen|first2=P.-Y.|last3=Bodde|first3=S. G.|last4=Yang|first4=W.|last5=Novitskaya|first5=E. E.|last6=Meyers|first6=M. A.|date=2012-04-03|title=The Structure, Functions, and Mechanical Properties of Keratin|journal=JOM|language=en|volume=64|issue=4|pages=449–468|doi=10.1007/s11837-012-0302-8|bibcode=2012JOM....64d.449M |s2cid=45028832 |issn=1047-4838}}

α-keratin synthesis begins near focal adhesions on the cell membrane. There, the keratin filament precursors go through a process known as nucleation, where the keratin precursors of dimers and filaments elongate, fuse, and bundle together. As this synthesis is occurring, the keratin filament precursors are transported by actin fibers in the cell towards the nucleus. There, the alpha-keratin intermediate filaments will collect and form networks of structure dictated by the use of the keratin cell as the nucleus simultaneously degrades.{{Cite journal|last1=Windoffer|first1=Reinhard|last2=Beil|first2=Michael|last3=Magin|first3=Thomas M.|last4=Leube|first4=Rudolf E.|date=2011-09-05|title=Cytoskeleton in motion: the dynamics of keratin intermediate filaments in epithelia|journal=The Journal of Cell Biology|language=en|volume=194|issue=5|pages=669–678|doi=10.1083/jcb.201008095|issn=0021-9525|pmid=21893596|pmc=3171125}} However, if necessary, instead of continuing to grow, the keratin complex will disassemble into non-filamentous keratin precursors that can diffuse throughout the cell cytoplasm. These keratin filaments will be able to be used in future keratin synthesis, either to re-organize the final structure or create a different keratin complex. When the cell has been filled with the correct keratin and structured correctly, it undergoes keratin stabilization and dies, a form of programmed cell death. This results in a fully matured, non-vascular keratin cell.{{Cite journal|last1=Kölsch|first1=Anne|last2=Windoffer|first2=Reinhard|last3=Würflinger|first3=Thomas|last4=Aach|first4=Til|last5=Leube|first5=Rudolf E.|date=2010-07-01|title=The keratin-filament cycle of assembly and disassembly|journal=J Cell Sci|language=en|volume=123|issue=13|pages=2266–2272|doi=10.1242/jcs.068080|issn=0021-9533|pmid=20554896|doi-access=free}} These fully matured, or cornified, alpha-keratin cells are the main components of hair, the outer layer of nails and horns, and the epidermis layer of the skin.{{Cite journal|last1=Eckhart|first1=Leopold|last2=Lippens|first2=Saskia|last3=Tschachler|first3=Erwin|last4=Declercq|first4=Wim|date=2013-12-01|title=Cell death by cornification|journal=Biochimica et Biophysica Acta (BBA) - Molecular Cell Research|volume=1833|issue=12|pages=3471–3480|doi=10.1016/j.bbamcr.2013.06.010|pmid=23792051|doi-access=}}

The property of most biological importance of alpha-keratin is its structural stability. When exposed to mechanical stress, α-keratin structures can retain their shape and therefore can protect what they surround.{{Cite journal|last1=Pan|first1=Xiaoou|last2=Hobbs|first2=Ryan P|last3=Coulombe|first3=Pierre A|year=2013|title=The expanding significance of keratin intermediate filaments in normal and diseased epithelia|journal=Current Opinion in Cell Biology|volume=25|issue=1|pages=47–56|doi=10.1016/j.ceb.2012.10.018|pmid=23270662|pmc=3578078}} Under high tension, the alpha-helix configuration of alpha-keratin can even change into beta-pleated sheets.{{Cite journal|last1=Kreplak|first1=L.|last2=Doucet|first2=J.|last3=Dumas|first3=P.|last4=Briki|first4=F.|date=2004-07-01|title=New Aspects of the α-Helix to β-Sheet Transition in Stretched Hard α-Keratin Fibers|pmc=1304386|journal=Biophysical Journal|language=en|volume=87|issue=1|pages=640–647|doi=10.1529/biophysj.103.036749|pmid=15240497|bibcode=2004BpJ....87..640K }} Not to be confused with beta-keratin which is a different protein. Alpha-keratin tissues also show signs of viscoelasticity, allowing them to both be able to stretch and absorb impact to a degree, though they are not impervious to fracture. Alpha-keratin strength is also affected by water content in the intermediate filament matrix; higher water content decreases the strength and stiffness of the keratin cell due to their effect on the various hydrogen bonds in the alpha-keratin network.

Alpha-keratins proteins can be one of two types: type I or type II. There are 54 keratin genes in humans, 28 of which code for type I, and 26 for type II.{{Cite journal|last1=Moll|first1=Roland|last2=Divo|first2=Markus|last3=Langbein|first3=Lutz|date=2017-03-07|title=The human keratins: biology and pathology|journal=Histochemistry and Cell Biology|volume=129|issue=6|pages=705–733|doi=10.1007/s00418-008-0435-6|issn=0948-6143|pmc=2386534|pmid=18461349}} Type I proteins are acidic, meaning they contain more acidic amino acids, such as aspartic acid, while type II proteins are basic, meaning they contain more basic amino acids, such as lysine.{{Cite journal|last1=Strnad|first1=Pavel|last2=Usachov|first2=Valentyn|last3=Debes|first3=Cedric|last4=Gräter|first4=Frauke|last5=Parry|first5=David A. D.|last6=Omary|first6=M. Bishr|date=2011-12-15|title=Unique amino acid signatures that are evolutionarily conserved distinguish simple-type, epidermal and hair keratins|journal=Journal of Cell Science|volume=124|issue=24|pages=4221–4232|doi=10.1242/jcs.089516|issn=0021-9533|pmc=3258107|pmid=22215855}} This differentiation is especially important in alpha-keratins because in the synthesis of its sub-unit dimer, the coiled coil, one protein coil must be type I, while the other must be type II. Even within type I and II, there are acidic and basic keratins that are particularly complementary within each organism. For example, in human skin, K5, a type II alpha keratin, pairs primarily with K14, a type I alpha-keratin, to form the alpha-keratin complex of the epidermis layer of cells in the skin.{{Cite journal|last1=Lee|first1=Chang-Hun|last2=Coulombe|first2=Pierre A.|date=2009-08-10|title=Self-organization of keratin intermediate filaments into cross-linked networks|journal=The Journal of Cell Biology|language=en|volume=186|issue=3|pages=409–421|doi=10.1083/jcb.200810196|issn=0021-9525|pmc=2728393|pmid=19651890}}

Hard alpha-keratins, such as those found in nails, have a higher cysteine content in their primary structure. This causes an increase in disulfide bonds that are able to stabilize the keratin structure, allowing it to resist a higher level of force before fracture. On the other hand, soft alpha-keratins, such as ones found in the skin, contain a comparatively smaller amount of disulfide bonds, making their structure more flexible.

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Category:Keratins