Investigation of coiled-coils as fusion protein surface mimics

ORGN 721

Philip Travisano, travp@lamar.colostate.edu and Alan J. Kennan, kennan@lamar.colostate.edu. Department of Chemistry, Colorado State University, Fort Collins, CO 80523
Alpha helical coiled-coils, formed by supercoiling of two or more component polypeptide strands, are ubiquitous mediators of biological structure and function. Recently we have described methods for controlling the assembly of 1:1:1 heterotrimeric coiled-coils using only interior hydrophobic core residue steric matching. This strategy affords maximal sequence flexibility in the patterning of exterior surface residues, which we have exploited to create mimics of therapeutically significant protein-protein interfaces. The HIV envelope protein gp41 facilitates infection by promoting fusion of cellular and viral membranes. At the heart of its function is formation of a trimer-of-hairpins structure in which a C-terminal ligand peptide binds to an N-terminal coiled-coil surface. This interaction is reminiscent of those in numerous other viral systems. The design of protein mimics by installation of key contact residues onto heterotrimeric coiled-coils will be discussed.
 

Asymmetric Reactions, Molecular Recognition, Self Assembly, Bioorganic Chemistry, Process R&D
8:00 PM-10:00 PM, Wednesday, 16 March 2005 Convention Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 14 March 2005 Convention Center -- Sails Pavilion, Sci-Mix

Division of Organic Chemistry

The 229th ACS National Meeting, in San Diego, CA, March 13-17, 2005