Abstract
Biological membranes are densely packed with membrane proteins that occupy approximately half of their volume. In almost all cases, membrane proteins in the native state lack the higher-order symmetry required for their direct study by diffraction methods. Despite many technical difficulties, numerous crystal structures of detergent solubilized membrane proteins have been determined that illustrate their internal organization. Among such proteins, class A G protein-coupled receptors have become amenable to crystallization and high resolution X-ray diffraction analyses. The derived structures of native and engineered receptors not only provide insights into their molecular arrangements but also furnish a framework for designing and testing potential models of transformation from inactive to active receptor signaling states and for initiating rational drug design.
Footnotes
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This research was supported by National Institutes of Health grants EY09339, GM079191, and by an unrestricted grant from Amgen Inc and Sandler Program for Asthma Research. D.M. was supported in part by the CWRU Medical Scientist Training Program (MSTP) and National Institutes of Health grant T32-GM007250.
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ABBREVIATIONS: GPCR, G protein-coupled receptor; MII, metarhodopsin II; MI, metarhodopsin I; CGS21680, 2-[p-(2-carboxyethyl)phenethyl-amino]-5′-N-ethylcarboxamidoadenosine; AR, adrenergic receptor; ZM241385, 4-{2-[7-amino-2-(2-furyl)[1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-ylamino]ethyl}phenol.
- Received September 9, 2008.
- Accepted October 21, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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