西亚试剂优势供应上万种化学试剂产品，欢迎各位新老客户咨询、选购！
中国
联系我们
联系方式：400-990-3999 / 邮箱：sales@xiyashiji.com
西亚试剂 —— 品质可靠，值得信赖
GPCR Engineering Yields High-Resolution Structural Insights into 
2 Adrenergic Receptor Function
Daniel M. Rosenbaum 1
, Vadim Cherezov 2, Michael A. Hanson 2, Søren G. F. Rasmussen 1, Foon Sun Thian 1, Tong Sun Kobilka 1, Hee-Jung Choi 3, Xiao-Jie Yao 1, William I. Weis 3, Raymond C. Stevens 2*, Brian K. Kobilka 1*
1 Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
2 Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
3 Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
* To whom correspondence should be addressed.
Raymond C. Stevens , E-mail:
The
These authors contributed equally to this work. 
2 adrenergic receptor (2AR) is a well-studied prototype for G protein-coupled receptors (GPCRs) that respond to diffusible hormones and neurotransmitters. To overcome the structural flexibility of the 2AR and to facilitate its crystallization, we engineered a 2AR fusion protein in which T4 Lysozyme replaces most of the third intracellular loop of the GPCR ("2AR-T4L"), and showed that this protein retains near-native pharmacologic properties. Analysis of adrenergic receptor ligand-binding mutants within the context of the reported high-resolution structure of 2AR-T4L provides insights into inverse agonist binding and structural changes required to accommodate catecholamine agonists. Amino acids known to regulate receptor function are linked through packing interactions and a network of hydrogen bonds, suggesting a conformational pathway from the ligand-binding pocket to regions that interact with G proteins.
