Oligomerization and folding in membrane proteins
We are interested in how the primary sequences of membrane proteins determine their three dimensional structures, and hence their functions. The folding of integral membrane proteins clearly differs from that of soluble proteins since the membrane environment imposes constraints on polypeptide secondary and tertiary structural features quite different from those imposed by an aqueous environment.A conceptual underpinning for much of the work in the group is that, for helical transmembrane proteins, the protein folding process can be considered to occur in two kinetically separated and therefore energetically distinct stages. First, transbilayer alpha-helices are formed (stage I) and second, the helices interact within the bilayer to form a specific globular tertiary structure (stage II).
In the case of oligomerization events, monomeric proteins are synthesized and inserted into the membrane, and these monomers subsequently interact in a side-to-side fashion to form complexes that involve helix-helix interactions similar to those found within polytopic helical membrane proteins.
Our work is supported by grants from the NIH: GM073857 and CA133890 (collaboration with the University of Rhode Island).
