Crystallin

The main function of crystallins at least in the lens of the eye is probably to increase the refractive index while not obstructing light. However, this is not their only function. It has become clear that crystallins may have several metabolic and regulatory functions, both within the lens and in other parts of the body.{{Cite book

| author = Bhat SP

| chapter = Crystallins, genes and cataract

| title = Progress in Drug Research

| series= Progress in Drug Research. Fortschritte der Arzneimittelforschung. Progres des Recherches Pharmaceutiques

| volume = 60

| pages = 205–262

| year = 2003

| doi = 10.1007/978-3-0348-8012-1_7

| pmid = 12790344

| isbn = 978-3-0348-9402-9

}} More proteins containing βγ-crystallin domains have now been characterized as calcium binding proteins with Greek key motif as a novel calcium-binding motif.[https://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=betagamma-crystallin+AND+calcium&log$=activity betagamma-crystallin AND calcium - PubMed result]

Some crystallins are active enzymes, while others lack activity but show homology to other enzymes.{{Cite journal

| vauthors = Jörnvall H, Persson B, Du Bois GC, Lavers GC, Chen JH, Gonzalez P, Rao PV, ((Zigler JS Jr))

| title = Zeta-crystallin versus other members of the alcohol dehydrogenase super-family. Variability as a functional characteristic

| journal = FEBS Letters

| volume = 322

| issue = 3

| pages = 240–244

| year = 1993

| pmid = 8486156 | doi=10.1016/0014-5793(93)81578-N

| s2cid = 562775

| doi-access = free

| bibcode = 1993FEBSL.322..240J

}}{{Cite journal

| vauthors =Rao PV, Krishna CM, ((Zigler JS Jr))

| title = Identification and characterization of the enzymatic activity of zeta-crystallin from guinea pig lens. A novel NADPH:quinone oxidoreductase

| journal = The Journal of Biological Chemistry

| volume = 267

| issue = 1

| pages = 96–102

| year = 1992

| doi = 10.1016/S0021-9258(18)48464-5

| pmid = 1370456

| doi-access = free

}} The crystallins of different groups of organisms are related to a large number of different proteins, with those from birds and reptiles related to lactate dehydrogenase and argininosuccinate lyase, those of mammals to alcohol dehydrogenase and quinone reductase, and those of cephalopods to glutathione S-transferase and aldehyde dehydrogenase. Whether these crystallins are products of a fortuitous accident of evolution, in that these particular enzymes happened to be transparent and highly soluble, or whether these diverse enzymatic activities are part of the protective machinery of the lens, is an active research topic.{{Cite journal

| author = Piatigorsky J

| title = Puzzle of crystallin diversity in eye lenses

| doi = 10.1002/aja.1001960408

| journal = Developmental Dynamics

| volume = 196

| issue = 4

| pages = 267–272

| year = 1993

| pmid = 8219350

| pmc =

| s2cid = 45840536

| doi-access =

}} The recruitment of protein that originally evolved with one function to serve a second, unrelated function is an example of an exaptation.{{Cite journal

| doi = 10.1037/0003-066X.53.5.533

| vauthors = Buss DM, Haselton MG, Shackelford TK, Bleske AL, Wakefield JC

| title = Adaptations, exaptations, and spandrels

| journal = The American Psychologist

| volume = 53

| issue = 5

| pages = 533–548

| year = 1998

| pmid = 9612136

| s2cid = 11128780

}}

File:AlignmentHumanCrystallinABG.PNG

Crystallins from a vertebrate eye lens are classified into three main types: alpha, beta and gamma crystallins. These distinctions are based on the order in which they elute from a gel filtration chromatography column. These are also called ubiquitous crystallins. Beta- and gamma-crystallins (such as CRYGC) are similar in sequence, structure and domains topology, and thus have been grouped together as a protein superfamily called βγ-Crystallins. The α-crystallin family and βγ-crystallins compose the major family of proteins present in the crystalline lens. They occur in all vertebrate classes (though gamma-crystallins are low or absent in avian lenses); and delta-crystallin is found exclusively in reptiles and birds.{{cite journal |doi=10.1016/0968-0004(89)90009-1 |vauthors=de Jong WW, Bloemendal H, Hendriks W, Mulders JW |title=Evolution of eye lens crystallins: the stress connection |journal=Trends Biochem. Sci. |volume=14 |issue=9 |pages=365–8 |year=1989 |pmid=2688200}}{{cite journal |doi=10.1038/nsb1094-724 |vauthors=Simpson A, Bateman O, Driessen H, Lindley P, Moss D, Mylvaganam S, Narebor E, Slingsby C |title=The structure of avian eye lens delta-crystallin reveals a new fold for a superfamily of oligomeric enzymes |journal=Nat. Struct. Biol. |volume=1 |issue=10 |pages=724–734 |year=1994 |pmid=7634077|s2cid=38532468 }}

In addition to these crystallins there are other taxon-specific crystallins which are only found in the lens of some organisms; these include delta, epsilon, tau, and iota-crystallins. For example, alpha, beta, and delta crystallins are found in avian and reptilian lenses, and the alpha, beta, and gamma families are found in the lenses of all other vertebrates.

{{Infobox protein family

| Symbol = Crystallin

| Name = Alpha crystallin A chain, N terminal

| image =

| width =

| caption =

| Pfam= PF00525

| InterPro= IPR003090

| SMART=

| Prosite =

| SCOP =

| TCDB =

| OPM family=

| OPM protein=

}}

Alpha-crystallin occurs as large aggregates, comprising two types of related subunits (A and B) that are highly similar to the small (15-30kDa) heat shock proteins (sHsps), particularly in their C-terminal halves. The relationship between these families is one of classic gene duplication and divergence, from the small HSP family, allowing adaptation to novel functions. Divergence probably occurred prior to evolution of the eye lens, alpha-crystallin being found in small amounts in tissues outside the lens.

Alpha-crystallin has chaperone-like properties including the ability to prevent the precipitation of denatured proteins and to increase cellular tolerance to stress.{{cite journal |author=Augusteyn RC |title=alpha-crystallin: a review of its structure and function |journal=Clin Exp Optom |volume=87 |issue=6 |pages=356–66 |year=2004 |doi=10.1111/j.1444-0938.2004.tb03095.x |pmid=15575808|s2cid=72202184 |doi-access= }} It has been suggested that these functions are important for the maintenance of lens transparency and the prevention of cataracts.{{cite journal |vauthors=Maulucci G, Papi M, Arcovito G, De Spirito M |title=The Thermal Structural Transition of α-Crystallin Inhibits the Heat Induced Self-Aggregation |journal=PLOS ONE |volume=6 |issue=5 |pages=e18906 |year=2011 |doi=10.1371/journal.pone.0018906 |pmid=21573059 |pmc=3090392|bibcode=2011PLoSO...618906M |doi-access=free }} This is supported by the observation that alpha-crystallin mutations show an association with cataract formation.

The N-terminal domain of alpha-crystallin is not necessary for dimerisation or chaperone activity, but appears to be required for the formation of higher order aggregates.{{cite journal |author=Augusteyn RC |title=alpha-Crystallin polymers and polymerization: the view from down under |journal=Int. J. Biol. Macromol. |volume=22 |issue=3 |pages=253–62 |year=1998 |doi=10.1016/S0141-8130(98)00023-3 |pmid=9650080}}{{cite journal |vauthors=Malfois M, Feil IK, Hendle J, Svergun DI, van Der Zandt H |title=A novel quaternary structure of the dimeric alpha-crystallin domain with chaperone-like activity |journal=J. Biol. Chem. |volume=276 |issue=15 |pages=12024–12029 |year=2001 |pmid=11278766 |doi=10.1074/jbc.M010856200|doi-access=free }}

{{Infobox protein family

| Symbol = Crystall

| Name = Beta/Gamma crystallin

| image =

| width =

| caption =

| Pfam= PF00030

| InterPro= IPR001064

| SMART=

| Prosite = PDOC00197

| SCOP = 4gcr

| TCDB =

| OPM family=

| OPM protein=

}}

Beta- and gamma- crystallin form a separate family.{{cite journal |author=Wistow G |title=Evolution of a protein superfamily: relationships between vertebrate lens crystallins and microorganism dormancy proteins |journal=J. Mol. Evol. |volume=30 |issue=2 |pages=140–145 |year=1990 |pmid=2107329 | doi = 10.1007/BF02099940 |bibcode=1990JMolE..30..140W |s2cid=1411821 |url=https://zenodo.org/record/1232520 }}{{cite journal |vauthors=Schoenmakers JG, Lubsen NH, Aarts HJ |title=The evolution of lenticular proteins: the beta- and gamma-crystallin super gene family |journal=Prog. Biophys. Mol. Biol. |volume=51 |issue=1 |pages=47–76 |year=1988 | doi=10.1016/0079-6107(88)90010-7 |pmid=3064189|doi-access=free }} Structurally, beta and gamma crystallins are composed of two similar domains which, in turn, are each composed of two similar motifs with the two domains connected by a short connecting peptide. Each motif, which is about forty amino acid residues long, is folded in a distinctive Greek key pattern. However, beta crystallin is an oligomer, composed of a complex group of molecules, whereas gamma crystallin is a simpler monomer.{{cite book |author=Nathaniel Knox Cartwright |author2=Petros Carvounis |title=Short answer questions for the MRCOphth, Part 1 |url=https://books.google.com/books?id=5KslZLOs58gC&pg=PA80 |year=2005 |publisher=Radcliffe Publishing |page=80 |isbn=9781857758849 }}{{Citation | last1 = Ghosh | first1 = Kalyan Sundar | last2 = Chauhan | first2 = Priyanka | title = Macromolecular Protein Complexes II: Structure and Function | publisher = Springer International Publishing | series = Subcellular Biochemistry | volume = 93| chapter = Crystallins and Their Complexes | date = 2019 | pages = 439–460 | url = https://doi.org/10.1007/978-3-030-28151-9_14 | doi = 10.1007/978-3-030-28151-9_14| pmid = 31939160 | isbn = 978-3-030-28151-9}}

{{cleanup section|reason=Lots of duplicate entries in the table. Please regenerate the table using only the "reviewed" entries.|date=March 2021}}

{{Reflist|30em}}

{{refbegin}}

• {{Cite journal

| author = Graw J

| title = The crystallins: Genes, proteins and diseases

| journal = Biological Chemistry

| volume = 378

| issue = 11

| pages = 1331–1348

| year = 1997

| pmid = 9426193

| doi=10.1515/bchm.1997.378.11.1299

}}

{{refend}}

• {{MeshName|Crystallins}}
• {{MeshName|alpha-Crystallins}}
• [http://sirtophamhatt.cryst.bbk.ac.uk/bca/CNews/1998/Dec98/eyeln.html Lens Crystallin Crystal Structures]{{dead link|date=August 2017 |bot=InternetArchiveBot |fix-attempted=yes }} by Christine Slingsby, Birkbeck College
• [http://www.rcsb.org/pdb/101/motm.do?momID=127 Crystallins: Molecule of the Month] {{Webarchive|url=https://web.archive.org/web/20151025082725/http://www.rcsb.org/pdb/101/motm.do?momID=127 |date=2015-10-25 }}, by David Goodsell, RCSB Protein Data Bank

{{Eye proteins}}

Category:Structural proteins

Category:Moonlighting proteins

Category:Human eye anatomy