Book of Abstracts: Albany 2005

category image Volume 22
No. 6
June 2005

Modulation and De Novo Design of Protein-Protein Interactions

All major cellular processes depend on the precise, highly specific self-assembly of proteins into functional units. Understanding and controlling the physical/chemical parameters that drive protein association is a major goal of protein biochemistry. To date, much progress has been made in this area by analyzing the large body of data collected on naturally occurring protein-protein interfaces. The field of protein design is uniquely positioned to complement these efforts with an inverse approach. That is, instead of analyzing and/or predicting the structures of native complexes, we can explore the physical chemistry of self-assembly through the modulation of naturally occurring protein-protein interfaces and through the de novo design of self-assembling protein complexes. The ability to direct a designed protein to bind to a target protein in a site-specific manner has potential therapeutic as well as other technological applications.

Here we report recent progress in modulating the binding specificity of calmodulin (a naturally occurring protein involved in regulating the activity of a large number of proteins via calcium mediated binding interactions) and in designing de novo protein-protein homo- and hetero-dimers from naturally occurring monomeric proteins. A highly interdisciplinary approach will be described that includes large-scale computation, experimentally determined binding affinities, and NMR and X-ray crystallographic structure analysis.

Stephen L. Mayo

Professor of Biology and Chemistry, Caltech
Howard Hughes Medical Institute
1200 E. California Blvd, mail code 114-96
Pasadena, CA 91125-7500

Phone: 626-395-6408
Fax: 626- 568-0934
Email: steve@mayo.caltech.edu