The Alpha Crystallins are ~20 kDa small heat shock proteins (sHSP) that play several important roles in the eye. There are two expressed forms of Alpha Crystallin, Alpha Crystallin A (aXA) and Alpha Crystallin B (aXB). Our lab will be focusing on aXB. Alpha Crystallin B is well conserved and plays two important and overlapping roles. First, it is a small heat shock protein that prevents misfolded proteins from aggregating in the lens of the eye. This delays or prevents the formation of cataracts, the number one cause of blindness in the world. Second, the protein takes part in a diverse oligomerization with other crystallins in the lens. This oligomerization is mediated by several protein-protein interaction surfaces in alpha crystallin. The Eisenberg Lab recently solved the crystal structure of most of this protein that showed these interation surfaces, and hinted at implications of its domain swapped C-terminal strand.
With leadership from post-doc Dr. Jim Hebda, our lab has focused on two important questions. First, what is the mechanism of chaperone function. To this end we will study model aggregation systems such as the insulin B-chain. Second, how does each of protein--protein interface contribute to oligomer stability and chaperone function. We will study the oligomerization of the alpha crystallins and the importance of each of the protein-protein interfaces by a variety of techniques. Our work studying the mechanism of chaperone function will inform the design and interpretation of results as we probe the importance of each oligomerization interface.