Crystallin

From Wikipedia, the free encyclopedia
  (Redirected from Alpha crystallin)
Jump to: navigation, search
Not to be confused with Crystalline.

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] Since it has been shown that lens injury may promote nerve regeneration,[4] 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.[5]

Function[edit]

The main function of crystallins at least in the lens of the eye is probably to increase the refractive index while not obstructing light [6]. However, this is not their only function. It is becoming increasingly 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[edit]

Interestingly and perhaps excitingly from an evolutionary perspective, 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.

Classification[edit]

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[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 (HSPs), 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
SCOP 4gcr
SUPERFAMILY 4gcr

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]


List of Human Crystallins [22]

List of Human Crystallins
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]

  1. ^ 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.  edit
  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.  edit
  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.  edit
  4. ^ 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.  edit
  5. ^ 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.  edit
  6. ^ Mahendiran K, Elie C, Nebel J-C, Ryan A, Pierscionek BK (2014) Primary sequence contribution to optical function of the eye lens, Scientific Reports, 4, 5195.
  7. ^ Bhat SP (2003). "Crystallins, genes and cataract". Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques 60: 205–262. PMID 12790344.  edit
  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. doi:10.1016/0014-5793(93)81578-N. PMID 8486156.  edit
  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. PMID 1370456.  edit
  11. ^ Piatigorsky J (1993). "Puzzle of crystallin diversity in eye lenses". Developmental Dynamics 196 (4): 267–272. doi:10.1002/aja.1001960408. PMID 8219350.  edit
  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.  edit
  13. ^ 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. 
  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. 
  15. ^ Augusteyn RC (2004). "alpha-crystallin: a review of its structure and function". Clin Exp Optom 87 (6): 356–66. PMID 15575808. 
  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. doi:10.1371/journal.pone.0018906. 
  17. ^ Augusteyn RC (1998). "alpha-Crystallin polymers and polymerization: the view from down under". Int. J. Biol. Macromol. 22 (3): 253–62. PMID 9650080. 
  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. doi:10.1007/BF02099940. PMID 2107329. 
  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. 
  22. ^ "Uniprot". 

Further reading[edit]

  • Graw J (1997). "The crystallins: Genes, proteins and diseases". Biological chemistry 378 (11): 1331–1348. PMID 9426193.  edit

External links[edit]