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Nat Rev Drug Discov. 2013 Jan;12(1):25-34. doi: 10.1038/nrd3859. Epub 2012 Dec 14.

The GPCR Network: a large-scale collaboration to determine human GPCR structure and function.

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Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.


G protein-coupled receptors (GPCRs) are targeted by ∼30-40% of marketed drugs, and their key roles in normal physiology and in disease demonstrate that an understanding of their structure and function is valuable to researchers in both basic science and drug discovery. However, until recently, detailed structural information on this protein family was limited by challenges in X-ray crystallographic analysis of such membrane proteins. The GPCR Network was created in 2010 with the goal of structurally characterizing 15-25 representative human GPCRs within 5 years, based on an active outreach programme addressing an interdisciplinary community of scientists interested in GPCR structure, chemistry and biology. Here, we provide an overview of how this collaborative effort has enabled the structural determination and characterization of eight human GPCRs so far, and discuss some of the challenges that remain in gaining more detailed insights into structure-function relationships in this receptor superfamily.

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