A Usual G-Protein-Coupled Receptor in Unusual Membranes

Udeep Chawla, Yunjiang Jiang, Wan Zheng, Liangju Kuang, Suchithranga M.D.C. Perera, Michael C. Pitman, Michael F. Brown, Hongjun Liang

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

G-protein-coupled receptors (GPCRs) are the largest family of membrane-bound receptors and constitute about 50 % of all known drug targets. They offer great potential for membrane protein nanotechnologies. We report here a charge-interaction-directed reconstitution mechanism that induces spontaneous insertion of bovine rhodopsin, the eukaryotic GPCR, into both lipid- and polymer-based artificial membranes. We reveal a new allosteric mode of rhodopsin activation incurred by the non-biological membranes: The cationic membrane drives a transition from the inactive MI to the activated MII state in the absence of high [H+] or negative spontaneous curvature. We attribute this activation to the attractive charge interaction between the membrane surface and the deprotonated Glu134 residue of the rhodopsin-conserved ERY sequence motif that helps break the cytoplasmic "ionic lock". This study unveils a novel design concept of non-biological membranes to reconstitute and harness GPCR functions in synthetic systems.

Original languageEnglish (US)
Pages (from-to)588-592
Number of pages5
JournalAngewandte Chemie - International Edition
Volume55
Issue number2
DOIs
StatePublished - Jan 11 2016

Keywords

  • G-protein-coupled receptor
  • biophysics
  • flexible surface model
  • photoactivation
  • rhodopsin

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Fingerprint Dive into the research topics of 'A Usual G-Protein-Coupled Receptor in Unusual Membranes'. Together they form a unique fingerprint.

Cite this