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 journalArticle

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

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Keywords

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

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Cite this

Chawla, U., Jiang, Y., Zheng, W., Kuang, L., Perera, S. M. D. C., Pitman, M. C., Brown, M. F., & Liang, H. (2016). A Usual G-Protein-Coupled Receptor in Unusual Membranes. Angewandte Chemie - International Edition, 55(2), 588-592. https://doi.org/10.1002/anie.201508648