Biophysical studies on the molecular chaperone function, structure and interaction of eye lens protein a-crystallin - A Review

Protein Chemistry Laboratory, Department of Chemistry, Bose Institute, 9311, Acharya Prafulla Chandra Road, Kolkata-700 009, India Manuscript received 17 October 2011, accepted 20 October 2011 α-Crystallin is the major constituent protein of the eye lens of the vertebrates. It is an oligomeric protein having micelle like architecture. Ever since it was reported in early 90's that it possesses molecular chaperone like function which is crucial for the maintenance of the transparency of the eye lens, interests in understanding the mechanism of such function developed rapidly. Various laboratories have contributed towards understanding of the structure and function of this protein. Our group has been engaged to study specific problems related to this area. We undertook detailed study to understand the structure of bound substrates employing a combination of simple molecular biology and bio physical tools to show that α-crystallin recognizes early folding intermediates and bound substrates native-like structure. Our work showed that chaperone activity correlated fairly well with exposed surface hydrophobicity. We proved that temperature activation was not required for α-crystallin to function as chaperone as was proposed by others. Very importantly we demonstrated that some small molecules such as ATP can interact with a-crystallin to form weak associated chaperone-substrate complex that can play crucial role in increasing the thermodynamic stability and chaperone function and refractive properties of the lens. Some bivalent metal ions such as Zn2+ plays a very important role in the structure, stability and chaperone function of a-crystallin and such a sore has considerable physiological significance in understanding the cataract formation in the lens. This article is not intended to be a comprehensive account of all aspects of work done on this protein. But instead in this article we have reviewed primarily our work and mentioned the work done by others in these specific areas only