Functional elucidation and manipulation of calcium binding in archeal crystalline

Abstract

The and#946;and#947;-crystallin group of proteins are ubiquitous in nature and present vast functional newlinedichotomy across various taxa of evolution. Paired Greek-key motif, comprising eight antiparallel newlinebeta strands forms the common structure denominator of all the and#946;and#947;-crystallins. The newlinedomain organisation of and#946;and#947;-crystallins varies from single domain monomeric proteins to multi newlinedomain oligomers. While the structural architecture confers high innate domain stability to newlinethe proteins, the unique amino acid sequences consisting mostly of charged residues imparts newlinefunctional diversity to these proteins. Several of the and#946;and#947;-crystallins additionally bind Ca2+, newlinewhich expands the functional and structural complexity of this group. Nonetheless, these newlineproteins share a common ancestral precursor and are presumed to have evolved through a newlineseries of gene duplications and rational modifications to accommodate the functional needs in newlineliving cells. newlineThe and#946;and#947;-crystallins have featured in the realm of biological, biophysical and newlinebiochemical research by various groups for their unique features like optical properties, newlinedomain stability and high solubility, structural and functional aspects. Aggregation of and#946;and#947;- newlinecrystallins in the eye lenses has been attributed leading cause of blindness due to lens newlineopacification. Extensive studies are underway to explicate the molecular mechanisms newlineunderlying crystallin aggregation. Several crystallin chimeras have been designed to mimic newlinethe refractive properties of lens crystallin as a prelude to finding cure for cataracts. The role newlineof point mutations in alleviating structural stability and altering the functional traits of and#946;and#947;- newlinecrystallins has also been discussed in great detail in various research findings. newlineDespite extensive research on manifold of crystallin characteristics, what remains newlineobscure till date is the evolution of functional disparity amongst various crystallins, explicit newlinerole of Ca2+-binding that gained a momentous attention due to its precise locations on and#946;and#947;- newlinecrystallin domains, connection between the lens and non-lens crystallins and so on. With the newlineexplosive expansion of crystallin members being discovered from across various taxa of newlineorganisms, there is an inevitable need to classify the and#946;and#947;-crystallins in a more systematic newlinemanner based not merely on sequence and structure patterns, but on functional cadres. This newlinerequires a tremendous effort since sequence based functional prediction is often cumbersome newlineand crystallins lack sequence homology. newline