UC Irvine

This thesis examines the properties of the human crystallin eye lens proteins from threeangles, how the structure of γS-crystallin relates to aggregation propensity, how αB-crystallin select between aggregation prone variants, and the structure of the crystallins in a lens like hydrogel. The human crystallins are normally highly soluble and stable, as an evolved adaptation to maintain the transparency of the eye lens. This is due to the intrinsic stability of the proteins themselves and the chaperone ability of the α-crystallins. By studying the structure and biophysical properties of novel and cataract associated variants of γS-crystallin with respect to aggregation propensity and client-chaperone interactions, it was discovered that αB-crystallin can select between different aggregation prone and function preserving variants, as well as a disconnect between the structural features that lead to a loss in stability and selection as a client. In the eye lens the concentration of the crystallins can reach over 400 mg/mL. By examining pure γS-crystallin as it exists in a highly concentrated hydrogel it was discovered that the gel is formed by the protein forming into larger order oligomers in the form of filaments and amorphous domains, but the domains retain a high degree of liquid like character. Lastly the properties of the plant specific insert (PSI) from Drosera capensis were examined. It was discovered that this protein exhibits anti-microbial properties, likely stemming from the fact that PSI can destabilize cell membranes and readily forms complexes with lipids.