Protection of ζ-crystallin by α-crystallin under thermal stress

Cataract is one of the major causes of blindness worldwide. Several factors including post-translational modification, thermal and solar radiations promote cataractogenesis. The camel lens proteins survive very harsh desert conditions and resist cataractogenesis. The folding and aggregation mechanism of camel lens proteins are poorly characterized. The camel lens contains three ubiquitous crystallins (alpha-, beta-, and gamma-crystallin) and a novel protein (zeta-crystallin) in large amounts. In this study, a sequence similarity search of camel alpha-crystallin with that of other organisms showed that the camel alpha B-crystallin consists of an extended N-terminal domain. Our results indicate that camel alpha-crystallin efficiently prevented aggregation of zeta-crystallin, with or without an obligate cofactor up to 89 degrees C. It performed a quick and efficient holdase function irrespective of the unfolding stage or aggregation. Camel alpha-crystallin exhibits approximately 20% chaperone activity between 30 and 40 degrees C and is completely activated above 40 degrees C. Camel alpha-crystallin underwent a single reversible thermal transition without loss of beta-sheet secondary structure. Intrinsic tryptophan fluorescence and ANS binding experiments revealed two transitions which corresponded to activation of its chaperone function. In contrast to earlier studies, camel alpha-crystallin completely protected lens proteins during thermal stress. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

Camel lens proteins show resistance to cataractogenesis in harsh conditions, with α-crystallin playing a key role in preventing aggregation of ζ-crystallin at high temperatures, exhibiting significant chaperone activity.