A first full-length class B GPCR crystal structure reveals novel receptor activation mechanisms

- Structure of the full-length human glucagon receptor ignites new excitement in GPCR research

SHANGHAI, May 17, 2017 /PRNewswire/ -- A team of scientists from Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences has determined the high-resolution atomic structure of a full-length class B G-protein-coupled receptor (GPCR) that plays a key role in glucose homeostasis. In an article published online in Nature on May 17, 2017 titled "Structure of the full-length glucagon class B G-protein-coupled receptor", scientists at SIMM, in collaboration with several groups based in China, United States, the Netherlands and Denmark, provided a detailed molecular map of the full-length human glucagon receptor (GCGR) in complex with a negative allosteric modulator and the antigen-binding fragment of an inhibitory antibody. This study is published together in Nature with a companion paper led by colleagues at the iHuman Institute, ShanghaiTech University describing the glucagon-like peptide-1 receptor (GLP-1R).

http://mma.prnewswire.com/media/512896/Shanghai_Institute_of_Materia_Medica_Chinese_Academy_of_Sciences.jpg [http://mma.prnewswire.com/media/512896/Shanghai_Institute_of_Materia_Medica_Chinese_Academy_of_Sciences.jpg]

Class B GPCRs are essential to numerous physiological processes and serve as important drug targets for many human diseases such as type 2 diabetes, metabolic syndrome, osteoporosis, migraine, depression and anxiety. According to team leader and SIMM professor Dr. Beili Wu, "This GCGR structure provides a clear picture of a full-length class B GPCR at high resolution, and helps us understand how different domains cooperate in modulating the receptor function at the molecular level."

The most exciting finding of this study is that the linker region connecting the ECD and TMD of the receptor works together with an extracellular loop of the TMD to regulate peptide binding through conformational changes, serving like a modulator in receptor activation.

The researchers performed a series of functional studies to support the GCGR structure and confirm the interactions between different domains in modulating its functionality. "This study was carried out in a team effort with experts from different fields and different countries. International collaboration is of paramount importance in solving major problems in science nowadays," said Dr. Hualiang Jiang, Director of SIMM.

"The full-length GCGR structure not only expands our knowledge about GPCR signaling mechanisms, but also offers new opportunities in drug discovery targeting class B GPCRs," said Dr. Ming-Wei Wang, Director of the National Center for Drug Screening.

The study was funded by the National Basic Research Programs, the National Health and Family Planning Commission, the National Natural Science Foundation, Chinese Academy of Sciences and GPCR Consortium.

Photo - http://mma.prnewswire.com/media/512896/Shanghai_Institute_of_Materia_Medica_Chinese_Academy_of_Sciences.jpg [http://mma.prnewswire.com/media/512896/Shanghai_Institute_of_Materia_Medica_Chinese_Academy_of_Sciences.jpg]

CONTACT: Wu Beili, +86-138-1848-8963, beiliwu@simm.ac.cn

PR Newswire

Dit persbericht is via ANP Pers Support naar internationale (vak en online) media gestuurd. Heb je nieuws voor buitenlandse journalisten? Bekijk dan onze mogelijkheden of neem contact met ons op.

Andere persberichten van deze organisatie

Verstuur nu éénmalig een persbericht

Verstuur persberichten en beeldmateriaal naar redacties in binnen- en buitenland. Via het ANP-net, het internationale medianetwerk van PR Newswire of met een perslijst op maat.

Direct persbericht versturen
070 - 41 41 234