Membrane Protein Crystallography: Issues and Examples

Michael C. Wiener, Department of Molecular Physiology and Biological Physics, University of Virginia

The elucidation of integral membrane protein structures is a frontier area of modern structural biology. Integral membrane proteins comprise 15-30% of the open-reading frames (ORFs) of an organism.s genome, are the current (and likely future) target of the majority of drugs, and carry out many biological processes of fundamental import. However, nontrivial technical challenges have impeded progress in this field. One challenge is the production of suitable quantities of membrane proteins, especially eukaryotic membrane proteins, for crystallization. Another challenge is obtaining three-dimensional crystals of sufficient long-range order to permit structure determination. A critical consideration is that the entity being crystallized is a protein-detergent complex (PDC), i.e., a protein encircled by a torus of detergent molecules. Therefore, both protein and detergent properties impact the crystallization outcome. I will present an overview of methods utilized in membrane protein crystallization; relevant physical-chemical properties of detergents will be discussed. We have used the phase behavior of detergent solutions as a guide for the development of novel crystallization screens. Several instances of the utility of neutron scattering will also be mentioned. Illustrative examples from the work of my laboratory (and others) will be presented.

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