Crystallin

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. It has also been identified in other places such as the heart, and in aggressive breast cancer tumors. The physical origins of eye lens transparency and its relationship to cataract are an active area of research. Since it has been shown that lens injury may promote nerve regeneration, 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.

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. More proteins containing βγ-crystallin domains have now been characterized as calcium binding proteins with Greek key motif as a novel calcium-binding motif.betagamma-crystallin AND calcium - PubMed result

Enzyme activity and evolution

Some crystallins are active enzymes, while others lack activity but show homology to other enzymes. 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. These particular enzymes or some mutated forms happened to be transparent and highly soluble and thus potential building material for animal lenses. The recruitment of protein that originally evolved with one function to serve a second, unrelated function is an example of an exaptation.

While crystallins appear to have evolved from enzymes, most copies in the human genome have arisen from gene duplications. Most notably, there are 2 gene clusters in the human genome, one on chromosome 2 and one on chromosome 22.

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.

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 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. It has been suggested that these functions are important for the maintenance of lens transparency and the prevention of cataracts. 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.

Beta and gamma crystallin

Beta and gamma crystallins form a separate family. 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 crystallins are oligomers, composed of a complex group of molecules, whereas gamma crystallins are simpler monomers.

+ List of Human Crystallins 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 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

References

Crystallin

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