Agonist-bound structure of the human P2Y12 receptor

Jin Zhang, Kaihua Zhang, Zhan-Guo Gao, Silvia Paoletta, Dandan Zhang, Gye Won Han, Tingting Li, Limin Ma, Wenru Zhang, Christa E. Müller, Huaiyu Yang, Hualiang Jiang (+6 others)
2014 Nature  
Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms * To whom correspondence should be addressed: beiliwu@simm.ac.cn and zhaoq@simm.ac.cn. † These authors contributed equally to this work. Supplementary Information is linked to the online version of the paper at www.nature.com/nature. Author Contributions:
more » ... J.Z. optimized the construct, expressed and purified human P2Y 12 R-BRIL for crystallization, developed the purification procedure, performed crystallization trials, optimized crystallization conditions. K.Z. helped in construct and crystal opimization, and collected diffraction data. Z.G.G. designed, performed and analysed ligand binding and competition assays of wildtype and mutant P2Y 12 R. S.P. performed and analysed docking assays.D.Z. helped in expression and purification. G.W.H. solved and refined the structure. T.L. helped the expression for crystallization trials. L.M. helped the expression for the activity assays. W.Z. developed the initial expression and purification protocol for P2Y 12 R. C.E.M. helped to design and analyze pharmacological experiments and wrote the manuscript. H.Y. helped to design and analysed docking assays. H.J. oversaw design and validation of P2Y 12 R models. V.C. helped to design and optimize LCP crystallization trials, and processed crystallographic data and wrote the manuscript. V.K. performed and analysed molecular modeling simulations, and wrote the manuscript. K.A.J. oversaw, designed and analysed ligand binding assays and docking, and wrote the manuscript. R.C.S. oversaw expression, purification and crystallization, and structure analysis/interpretation of P2Y 12 R. B.W. and Q.Z. initiated the project, planned and analysed experiments, supervised the research and wrote the manuscript. Author information: Atomic coordinates and structure factors for the P2Y 12 R-2MeSADP and P2Y 12 R-2MeSATP structures have been deposited in the Protein Data Bank with identification codes 4PXZ and 4PY0, respectively. Reprints and permissions information is available at www.nature.com/reprints.
doi:10.1038/nature13288 pmid:24784220 pmcid:PMC4128917 fatcat:5uv7h4snubgsjjlvf53rscbzey