Submitted to: Experimental Eye Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/1/1995
Publication Date: N/A
Interpretive Summary: Alpha-crystallin is the major protein in eye lenses and exists in several forms. How this protein self-assembles determines whether the lens will be transparent or develop cataracts, leading to partial or total blindness. Previously, we constructed a predicted three-dimensional structure of the individual alpha-crystallins. In this study, we constructed a self-assembled superstructure which complies with all known experimental results. This information will benefit pharmacologists who are designing drugs for eliminating cataracts and nutritionists who are evaluating the nutritional requirements necessary for prevention of cataract development.
Technical Abstract: The quaternary structure of alpha-crystallin is the missing link for defining its functions as a structural and chaperone protein on the molecular level. Alpha-crystallin exists in the lens as polydisperse, dynamic heteropolymers with varying ratios of alpha A and alpha B subunits (-20kD). We constructed quaternary structures of both hetero- and homo- polymers of varying molecular weights by using computer generated working models of the two subunits and their complex. The elongate, amphipathic nature of these 3-D subunits is best suited for construction of a micellar quaternary structure. Orientation of each subunit is dictated by the assumption that interactions of the hydrophobic N-termini are the driving force for aggregation. The models are "open" spherical micelles which contain an inner cavity defined by the proximal, hydrophobic N-terminal residues. The observed graded increase in aggregate radius with increased molecular weight can be attibuted to increases in the diameter of the inner cavity. The hydrophilic C-terminal domain of each subunit is exposed to the surface and imparts aggregate solubility. These quaternary structures agree well with the vast literature that has accumulated over the past several decades.