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Biochemistry. 2013 Dec 3;52(48):8625-32. doi: 10.1021/bi401300y. Epub 2013 Nov 19.

Probing G protein-coupled receptor-ligand interactions with targeted photoactivatable cross-linkers.

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Laboratory of Chemical Biology and Signal Transduction, The Rockefeller University , 1230 York Avenue, New York , New York 10065, United States.


It has been 50 years since F. H. Westheimer and colleagues reported the first use of a photoactivatable cross-linking reagent to study the active site of chymotrypsin. In studies of seven transmembrane helical receptors, also known as G protein-coupled receptors (GPCRs), recent simultaneous advances in structural biology, molecular dynamics simulations, and amber codon suppression methods have allowed the development of a targeted photo-cross-linking strategy to probe receptor-ligand interactions in cell membranes. We review here recent advances in targeted photo-cross-linking of GPCR-ligand complexes in the context of extensive earlier work that primarily relied upon the use of ligand analogues with photoactivatable constituents.

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