濡木研公開ラボセミナー
Approaches to GPCR complex formation for structure determination by single particle cryo-EM
Lynn Liang 博士(Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University)
2018年06月26日(火) 14:00-15:00 理学部1号館東棟 380号室
G protein coupled receptors (GPCRs) are 7 transmembrane proteins that play vital roles in a range of biological processes. Class B GPCRs peptide hormone receptors are involved in obesity, type 2 diabetes, osteoporosis, migraine and cardiovascular disease. The progress of drug development for targeting these receptors are hindered by limited understanding of structure and mechanism of activation.
There has been significant development in both protein engineering and biophysical techniques that have led to an increasing number of GPCR structures. However, these are largely class A GPCRs and structures of fully-activated GPCRs in complex with cognate heterotrimeric G proteins have been limited. Preparation of stable GPCRs complex for structural determination remained challenging. Recent advances in structural techniques and complex stabilisation have facilitated structural determination of novel GPCR structures in complex with G protein. These structures provide valuable insight for class B GPCR activation.