Crystallin

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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]

Contents

Function

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. [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

Some 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]

An alignment of the human crystallin proteins alpha, beta, and gamma from Uniprot. AlignmentHumanCrystallinABG.PNG
An alignment of the human crystallin proteins alpha, beta, and gamma from Uniprot.

Classification

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. [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

Alpha crystallin A chain, N terminal
Identifiers
SymbolCrystallin
Pfam PF00525
InterPro IPR003090
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

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

Beta/Gamma crystallin
Identifiers
SymbolCrystall
Pfam PF00030
InterPro IPR001064
PROSITE PDOC00197
SCOP2 4gcr / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

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]

List of Human Crystallins [23]
UniProt Entry nameAlternate Gene namesLength
AIM1L_HUMANAIM1L CRYBG2616
AIM1_HUMANAIM1 CRYBG11723
ARLY_HUMANASL464
CRBA1_HUMANCRYBA1 CRYB1215
CRBA2_HUMANCRYBA2197
CRBB1_HUMANCRYBB1252
CRBA4_HUMANCRYBA4196
CRBB2_HUMANCRYBB2 CRYB2 CRYB2A205
CRBB3_HUMANCRYBB3 CRYB3211
CRBG3_HUMANCRYBG31022
CRBS_HUMANCRYGS CRYG8178
CRGA_HUMANCRYGA CRYG1174
CRGC_HUMANCRYGC CRYG3174
CRGB_HUMANCRYGB CRYG2175
CRGN_HUMANCRYGN182
CRGD_HUMANCRYGD CRYG4174
CRYAA_HUMANCRYAA CRYA1 HSPB4173
CRYAB_HUMANCRYAB CRYA2175
CRYL1_HUMANCRYL1 CRY319
CRYM_HUMANCRYM THBP314
HSPB2_HUMANHSPB2182
HSPB3_HUMANHSPB3 HSP27 HSPL27150
HSPB8_HUMANHSPB8 CRYAC E2IG1 HSP22 PP1629196
HSPB7_HUMANHSPB7 CVHSP170
HSPB9_HUMANHSPB9159
HSPB1_HUMANHSPB1 HSP27 HSP28205
HSPB6_HUMANHSPB6160
IFT25_HUMANHSPB11 C1orf41 IFT25 HSPC034144
MAF_HUMANMAF373
ODFP1_HUMANODF1 ODFP250
QORL1_HUMANCRYZL1 4P11349
QOR_HUMANCRYZ329
TITIN_HUMANTTN34350
ZEB1_HUMANZEB1 AREB6 TCF81124
Q9UFA7_HUMANDKFZp434A0627 CRYGS hCG_16149120
B4DU04_HUMANAIM1 hCG_33516542
A8KAH6_HUMANHSPB2 hCG_39461182
Q6ICS9_HUMANHSPB3 hCG_1736006150
Q68DG0_HUMANDKFZp779D0968 HSPB7174
Q8N241_HUMANHSPB7 hCG_23506245
B4DLE8_HUMANCRYBG31365
C3VMY8_HUMANCRYAB175
R4UMM2_HUMANCRYBB2205
B3KQL3_HUMAN119
Q24JT5_HUMANCRYGA105
V9HWB6_HUMANHEL55160
B4DNC2_HUMAN196
V9HW27_HUMANHEL-S-101175
H0YCW8_HUMANCRYAB106
E9PHE4_HUMANCRYAA136
E9PNH7_HUMANCRYAB106
E7EWH7_HUMANCRYAA153
B4DL87_HUMAN170
V9HW43_HUMANHEL-S-102205
E9PR44_HUMANCRYAB174
Q8IVN0_HUMAN86
B7ZAH2_HUMAN542
C9J5A3_HUMANHSPB7124
E9PRS4_HUMANCRYAB69
K7EP04_HUMANHSPB6137
I3L3Y1_HUMANCRYM97
H0YG30_HUMANHSPB8152
H9KVC2_HUMANCRYM272
E9PS12_HUMANCRYAB77
E9PIR9_HUMANAIM1L787
B4DUL6_HUMAN80
I3NI53_HUMANCRYM140
Q9NTH7_HUMANDKFZp434L1713264
J3KQW1_HUMANAIM1L296
Q96QW7_HUMANAIM1316
I3L2W5_HUMANCRYM165
B1AHR5_HUMANCRYBB3113
B4DLI1_HUMAN403
I3L325_HUMANCRYM241
Q7Z3C1_HUMANDKFZp686A14192191
B4DWM9_HUMAN154
Q71V83_HUMANCRYAA69
Q6P5P8_HUMANAIM1326
C9JDH2_HUMANCRYBA2129
B4DIA6_HUMAN155
Q13684_HUMAN56
F8WE04_HUMANHSPB1186
J3QRT1_HUMANCRYBA175
E9PRA8_HUMANCRYAB155
E9PJL7_HUMANCRYAB130
C9J5N2_HUMANCRYBG3229
I3L3J9_HUMANCRYM26
C9J659_HUMANCRYBG3131
D3YTC6_HUMANHSPB7165

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References

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  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
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  8. ↑ betagamma-crystallin AND calcium - PubMed result
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. 1 2 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.
  14. ↑ 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.
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  16. ↑ 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.
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  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ Nathaniel Knox Cartwright; Petros Carvounis (2005). Short answer questions for the MRCOphth, Part 1. Radcliffe Publishing. p. 80. ISBN   9781857758849.
  22. ↑ 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
  23. ↑ "Uniprot".

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