In anatomy, a crystallin is a water-soluble structural protein found in the lens and the cornea of the eye accounting for the transparency of the structure.[1] It has also been identified in other places such as the heart, and in aggressive breast cancer tumors.[2][3] The physical origins of eye lens transparency and its relationship to cataract are an active area of research. [4] Since it has been shown that lens injury may promote nerve regeneration,[5] crystallin has been an area of neural research. So far, it has been demonstrated that crystallin β b2 (crybb2) may be a neurite-promoting factor.[6]
Function
editThe 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.[7] More proteins containing βγ-crystallin domains have now been characterized as calcium binding proteins with Greek key motif as a novel calcium-binding motif.[8]
Enzyme activity
editSome crystallins are active enzymes, while others lack activity but show homology to other enzymes.[9][10] 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.[11] The recruitment of protein that originally evolved with one function to serve a second, unrelated function is an example of an exaptation.[12]
Classification
editCrystallins 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.[13][14]
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.
Alpha-crystallin
edit| Alpha crystallin A chain, N terminal | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Crystallin | ||||||||
| Pfam | PF00525 | ||||||||
| InterPro | IPR003090 | ||||||||
| |||||||||
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.[13]
Alpha-crystallin has chaperone-like properties including the ability to prevent the precipitation of denatured proteins and to increase cellular tolerance to stress.[15] It has been suggested that these functions are important for the maintenance of lens transparency and the prevention of cataracts.[16] 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.[17][18]
Beta and gamma crystallin
edit| Beta/Gamma crystallin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Crystall | ||||||||
| Pfam | PF00030 | ||||||||
| InterPro | IPR001064 | ||||||||
| PROSITE | PDOC00197 | ||||||||
| SCOP2 | 4gcr / SCOPe / SUPFAM | ||||||||
| |||||||||
Beta- and gamma- crystallin form a separate family.[19][20] 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.[21] [22]
This section may require cleanup to meet Wikipedia's quality standards. The specific problem is: Lots of duplicate entries in the table. Please regenerate the table using only the "reviewed" entries. (March 2021) |
| UniProt Entry name | Alternate Gene names | Length |
|---|---|---|
| AIM1L_HUMAN | AIM1L CRYBG2 | 616 |
| AIM1_HUMAN | AIM1 CRYBG1 | 1723 |
| ARLY_HUMAN | ASL | 464 |
| CRBA1_HUMAN | CRYBA1 CRYB1 | 215 |
| CRBA2_HUMAN | CRYBA2 | 197 |
| CRBB1_HUMAN | CRYBB1 | 252 |
| CRBA4_HUMAN | CRYBA4 | 196 |
| CRBB2_HUMAN | CRYBB2 CRYB2 CRYB2A | 205 |
| CRBB3_HUMAN | CRYBB3 CRYB3 | 211 |
| CRBG3_HUMAN | CRYBG3 | 1022 |
| CRBS_HUMAN | CRYGS CRYG8 | 178 |
| CRGA_HUMAN | CRYGA CRYG1 | 174 |
| CRGC_HUMAN | CRYGC CRYG3 | 174 |
| CRGB_HUMAN | CRYGB CRYG2 | 175 |
| CRGN_HUMAN | CRYGN | 182 |
| CRGD_HUMAN | CRYGD CRYG4 | 174 |
| CRYAA_HUMAN | CRYAA CRYA1 HSPB4 | 173 |
| CRYAB_HUMAN | CRYAB CRYA2 | 175 |
| CRYL1_HUMAN | CRYL1 CRY | 319 |
| CRYM_HUMAN | CRYM THBP | 314 |
| HSPB2_HUMAN | HSPB2 | 182 |
| HSPB3_HUMAN | HSPB3 HSP27 HSPL27 | 150 |
| HSPB8_HUMAN | HSPB8 CRYAC E2IG1 HSP22 PP1629 | 196 |
| HSPB7_HUMAN | HSPB7 CVHSP | 170 |
| HSPB9_HUMAN | HSPB9 | 159 |
| HSPB1_HUMAN | HSPB1 HSP27 HSP28 | 205 |
| HSPB6_HUMAN | HSPB6 | 160 |
| IFT25_HUMAN | HSPB11 C1orf41 IFT25 HSPC034 | 144 |
| MAF_HUMAN | MAF | 373 |
| ODFP1_HUMAN | ODF1 ODFP | 250 |
| QORL1_HUMAN | CRYZL1 4P11 | 349 |
| QOR_HUMAN | CRYZ | 329 |
| TITIN_HUMAN | TTN | 34350 |
| ZEB1_HUMAN | ZEB1 AREB6 TCF8 | 1124 |
| Q9UFA7_HUMAN | DKFZp434A0627 CRYGS hCG_16149 | 120 |
| B4DU04_HUMAN | AIM1 hCG_33516 | 542 |
| A8KAH6_HUMAN | HSPB2 hCG_39461 | 182 |
| Q6ICS9_HUMAN | HSPB3 hCG_1736006 | 150 |
| Q68DG0_HUMAN | DKFZp779D0968 HSPB7 | 174 |
| Q8N241_HUMAN | HSPB7 hCG_23506 | 245 |
| B4DLE8_HUMAN | CRYBG3 | 1365 |
| C3VMY8_HUMAN | CRYAB | 175 |
| R4UMM2_HUMAN | CRYBB2 | 205 |
| B3KQL3_HUMAN | 119 | |
| Q24JT5_HUMAN | CRYGA | 105 |
| V9HWB6_HUMAN | HEL55 | 160 |
| B4DNC2_HUMAN | 196 | |
| V9HW27_HUMAN | HEL-S-101 | 175 |
| H0YCW8_HUMAN | CRYAB | 106 |
| E9PHE4_HUMAN | CRYAA | 136 |
| E9PNH7_HUMAN | CRYAB | 106 |
| E7EWH7_HUMAN | CRYAA | 153 |
| B4DL87_HUMAN | 170 | |
| V9HW43_HUMAN | HEL-S-102 | 205 |
| E9PR44_HUMAN | CRYAB | 174 |
| Q8IVN0_HUMAN | 86 | |
| B7ZAH2_HUMAN | 542 | |
| C9J5A3_HUMAN | HSPB7 | 124 |
| E9PRS4_HUMAN | CRYAB | 69 |
| K7EP04_HUMAN | HSPB6 | 137 |
| I3L3Y1_HUMAN | CRYM | 97 |
| H0YG30_HUMAN | HSPB8 | 152 |
| H9KVC2_HUMAN | CRYM | 272 |
| E9PS12_HUMAN | CRYAB | 77 |
| E9PIR9_HUMAN | AIM1L | 787 |
| B4DUL6_HUMAN | 80 | |
| I3NI53_HUMAN | CRYM | 140 |
| Q9NTH7_HUMAN | DKFZp434L1713 | 264 |
| J3KQW1_HUMAN | AIM1L | 296 |
| Q96QW7_HUMAN | AIM1 | 316 |
| I3L2W5_HUMAN | CRYM | 165 |
| B1AHR5_HUMAN | CRYBB3 | 113 |
| B4DLI1_HUMAN | 403 | |
| I3L325_HUMAN | CRYM | 241 |
| Q7Z3C1_HUMAN | DKFZp686A14192 | 191 |
| B4DWM9_HUMAN | 154 | |
| Q71V83_HUMAN | CRYAA | 69 |
| Q6P5P8_HUMAN | AIM1 | 326 |
| C9JDH2_HUMAN | CRYBA2 | 129 |
| B4DIA6_HUMAN | 155 | |
| Q13684_HUMAN | 56 | |
| F8WE04_HUMAN | HSPB1 | 186 |
| J3QRT1_HUMAN | CRYBA1 | 75 |
| E9PRA8_HUMAN | CRYAB | 155 |
| E9PJL7_HUMAN | CRYAB | 130 |
| C9J5N2_HUMAN | CRYBG3 | 229 |
| I3L3J9_HUMAN | CRYM | 26 |
| C9J659_HUMAN | CRYBG3 | 131 |
| D3YTC6_HUMAN | HSPB7 | 165 |
References
edit- ^ Jester JV (2008). "Corneal crystallins and the development of cellular transparency". Seminars in Cell & Developmental Biology. 19 (2): 82–93. doi:10.1016/j.semcdb.2007.09.015. PMC 2275913. PMID 17997336.
- ^ Lutsch G, Vetter R, Offhauss U, Wieske M, Gröne HJ, Klemenz R, Schimke I, Stahl J, Benndorf R (1997). "Abundance and location of the small heat shock proteins HSP25 and alphaB-crystallin in rat and human heart". Circulation. 96 (10): 3466–3476. doi:10.1161/01.cir.96.10.3466. PMID 9396443.
- ^ Moyano JV, Evans JR, Chen F, Lu M, Werner ME, Yehiely F, Diaz LK, Turbin D, Karaca G, Wiley E, Nielsen TO, Perou CM, Cryns VL (2005). "B-Crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer". Journal of Clinical Investigation. 116 (1): 261–270. doi:10.1172/JCI25888. PMC 1323258. PMID 16395408.
- ^ Panda, Alok Kumar; Nandi, Sandip Kumar; Chakraborty, Ayon; Nagaraj, Ram H.; Biswas, Ashis (1 January 2016). "Differential role of arginine mutations on the structure and functions of α-crystallin". Biochimica et Biophysica Acta (BBA) - General Subjects. 1860 (1, Part B): 199–210. doi:10.1016/j.bbagen.2015.06.004. PMC 4914040. PMID 26080000.
- ^ Fischer D, Pavlidis M, Thanos S (2000). "Cataractogenic lens injury prevents traumatic ganglion cell death and promotes axonal regeneration both in vivo and in culture". Investigative Ophthalmology & Visual Science. 41 (12): 3943–3954. PMID 11053298.
- ^ Liedtke T, Schwamborn JC, Schröer U, Thanos S (2007). "Elongation of Axons during Regeneration Involves Retinal Crystallin b2 (crybb2)". Molecular & Cellular Proteomics. 6 (5): 895–907. doi:10.1074/mcp.M600245-MCP200. PMID 17264069.
- ^ Bhat SP (2003). "Crystallins, genes and cataract". Progress in Drug Research. Progress in Drug Research. Fortschritte der Arzneimittelforschung. Progres des Recherches Pharmaceutiques. Vol. 60. pp. 205–262. doi:10.1007/978-3-0348-8012-1_7. ISBN 978-3-0348-9402-9. PMID 12790344.
- ^ betagamma-crystallin AND calcium - PubMed result
- ^ Jörnvall H, Persson B, Du Bois GC, Lavers GC, Chen JH, Gonzalez P, Rao PV, Zigler JS Jr (1993). "Zeta-crystallin versus other members of the alcohol dehydrogenase super-family. Variability as a functional characteristic". FEBS Letters. 322 (3): 240–244. Bibcode:1993FEBSL.322..240J. doi:10.1016/0014-5793(93)81578-N. PMID 8486156. S2CID 562775.
- ^ Rao PV, Krishna CM, Zigler JS Jr (1992). "Identification and characterization of the enzymatic activity of zeta-crystallin from guinea pig lens. A novel NADPH:quinone oxidoreductase". The Journal of Biological Chemistry. 267 (1): 96–102. doi:10.1016/S0021-9258(18)48464-5. PMID 1370456.
- ^ Piatigorsky J (1993). "Puzzle of crystallin diversity in eye lenses". Developmental Dynamics. 196 (4): 267–272. doi:10.1002/aja.1001960408. PMID 8219350. S2CID 45840536.
- ^ Buss DM, Haselton MG, Shackelford TK, Bleske AL, Wakefield JC (1998). "Adaptations, exaptations, and spandrels". The American Psychologist. 53 (5): 533–548. doi:10.1037/0003-066X.53.5.533. PMID 9612136. S2CID 11128780.
- ^ a b de Jong WW, Bloemendal H, Hendriks W, Mulders JW (1989). "Evolution of eye lens crystallins: the stress connection". Trends Biochem. Sci. 14 (9): 365–8. doi:10.1016/0968-0004(89)90009-1. PMID 2688200.
- ^ Simpson A, Bateman O, Driessen H, Lindley P, Moss D, Mylvaganam S, Narebor E, Slingsby C (1994). "The structure of avian eye lens delta-crystallin reveals a new fold for a superfamily of oligomeric enzymes". Nat. Struct. Biol. 1 (10): 724–734. doi:10.1038/nsb1094-724. PMID 7634077. S2CID 38532468.
- ^ Augusteyn RC (2004). "alpha-crystallin: a review of its structure and function". Clin Exp Optom. 87 (6): 356–66. doi:10.1111/j.1444-0938.2004.tb03095.x. PMID 15575808. S2CID 72202184.
- ^ Maulucci G, Papi M, Arcovito G, De Spirito M (2011). "The Thermal Structural Transition of α-Crystallin Inhibits the Heat Induced Self-Aggregation". PLOS ONE. 6 (5): e18906. Bibcode:2011PLoSO...618906M. doi:10.1371/journal.pone.0018906. PMC 3090392. PMID 21573059.
- ^ Augusteyn RC (1998). "alpha-Crystallin polymers and polymerization: the view from down under". Int. J. Biol. Macromol. 22 (3): 253–62. doi:10.1016/S0141-8130(98)00023-3. PMID 9650080.
- ^ Malfois M, Feil IK, Hendle J, Svergun DI, van Der Zandt H (2001). "A novel quaternary structure of the dimeric alpha-crystallin domain with chaperone-like activity". J. Biol. Chem. 276 (15): 12024–12029. doi:10.1074/jbc.M010856200. PMID 11278766.
- ^ Wistow G (1990). "Evolution of a protein superfamily: relationships between vertebrate lens crystallins and microorganism dormancy proteins". J. Mol. Evol. 30 (2): 140–145. Bibcode:1990JMolE..30..140W. doi:10.1007/BF02099940. PMID 2107329. S2CID 1411821.
- ^ Schoenmakers JG, Lubsen NH, Aarts HJ (1988). "The evolution of lenticular proteins: the beta- and gamma-crystallin super gene family". Prog. Biophys. Mol. Biol. 51 (1): 47–76. doi:10.1016/0079-6107(88)90010-7. PMID 3064189.
- ^ Nathaniel Knox Cartwright; Petros Carvounis (2005). Short answer questions for the MRCOphth, Part 1. Radcliffe Publishing. p. 80. ISBN 9781857758849.
- ^ Ghosh, Kalyan Sundar; Chauhan, Priyanka (2019), "Crystallins and Their Complexes", Macromolecular Protein Complexes II: Structure and Function, Subcellular Biochemistry, vol. 93, Springer International Publishing, pp. 439–460, doi:10.1007/978-3-030-28151-9_14, ISBN 978-3-030-28151-9, PMID 31939160
- ^ "Uniprot".
Further reading
edit- Graw J (1997). "The crystallins: Genes, proteins and diseases". Biological Chemistry. 378 (11): 1331–1348. doi:10.1515/bchm.1997.378.11.1299. PMID 9426193.
External links
edit- Crystallins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- alpha-Crystallins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Lens Crystallin Crystal Structures[permanent dead link] by Christine Slingsby, Birkbeck College
- Crystallins: Molecule of the Month Archived 2015-10-25 at the Wayback Machine, by David Goodsell, RCSB Protein Data Bank