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系统生物学研究中心学术报告:Structural Studies of Arrestin-Mediated GPCR Signaling

Structural Studies of Arrestin-Mediated GPCR Signaling

演讲人: X. Edward Zhou, Ph.D.
Senior Research Scientist
Laboratory of Structural Sciences, Van Andel Research Institute, USA

演讲内容:
G protein-coupled receptors (GPCRs) mediate diverse signaling through G proteins or arrestins. Arrestin binding to GPCRs promotes receptor internalization and signaling through G protein-independent pathways. High-affinity binding of arrestins to GPCRs requires receptor phosphorylation, often at the receptor’s C-terminal tail. We determined the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of mouse visual arrestin by serial femtosecond X-ray laser crystallography. The structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements including TM7, Helix 8 and particularly the phosphorylated C-terminal tail to recruit arrestin. The phospho-residues on the C-terminal tail of the receptor form an extensive network of electrostatic interactions with three positively charged pockets in arrestin. Based on these observations, we derived and validated a set of phosphorylation codes that serve as a molecular mechanism for phosphorylation-dependent recruitment of arrestins by GPCRs.

演讲者最近研究:
1. Understanding the GPCR biased signaling through G protein and arrestin complex structures. Curr Opin Struct Biol. 2017 Aug;45:150-159.
2. Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors.Cell. 2017 Jul 27;170(3):457-469.
3. Structural Basis of TPR-Mediated Oligomerization and Activation of Oncogenic Fusion Kinases. Structure. 2017 Jun 6;25(6):867-877.
4. An intrinsic agonist mechanism for activation of glucagon-like peptide-1 receptor by its extracellular domain. Cell Discov. 2016 Nov 22;2:16042. Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-ligase signaling effector DWARF3. Cell Res. 2015 Nov;25(11):1219-36.
5. Structural basis of JAZ repression of MYC transcription factors in jasmonate signalling. Nature. 2015 Sep 10;525(7568):269-73.
6. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature. 2015 Jul 30;523(7562):561-7.
7. Melcher K. Structural basis of AMPK regulation by adenine nucleotides and glycogen. Cell Res. 2015 Jan;25(1):50-66.
8. Structures and mechanism for the design of highly potent glucocorticoids. Cell Res. 2014 Jun;24(6):713-26.

主持人:沈百荣教授(苏州大学系统生物学研究中心,电子信息学院);

时间: 2018年3月14日下午4:00;
地点: 苏州大学本部纯水楼402;

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