W0020

Detergent Effects and Membrane Protein Crystallization: Rational Approaches to a Crazy Problem. Patrick J. Loll, Dept. of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104-6084, USA.

Membrane proteins are generally only crystallized after heroic efforts and/or massive expenditures of time and resources. We are studying the role of detergents in the crystallization of membrane proteins, with the hope of rationalizing and simplifying the crystallization process. When dissolved with detergents, integral membrane proteins form protein-detergent complexes (PDCs). We have shown that the interactions between the detergent moieties of PDCs can be exploited to facilitate crystal growth, and have identified specific molecular properties of detergents that are predictors of crystallization. This has led to the design of specialized membrane protein crystallization screens, which display a success rate of up to 20% in initial

tests. Strategies for optimization of these screens and for the application of high throughput methodologies to membrane protein crystallization will be discussed.