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

11 Citations (Scopus)

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

Fingerprint

G-Protein-Coupled Receptors
Proteins
Membranes
Rhodopsin
Chemical activation
Nanotechnology
Polymers
Membrane Proteins
Lipids
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis

Cite this

Chawla, U., Jiang, Y., Zheng, W., Kuang, L., Perera, S. M. D. C., Pitman, M. C., ... 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

A Usual G-Protein-Coupled Receptor in Unusual Membranes. / Chawla, Udeep; Jiang, Yunjiang; Zheng, Wan; Kuang, Liangju; Perera, Suchithranga M D C; Pitman, Michael C.; Brown, Michael F; Liang, Hongjun.

In: Angewandte Chemie - International Edition, Vol. 55, No. 2, 11.01.2016, p. 588-592.

Research output: Contribution to journalArticle

Chawla, U, Jiang, Y, Zheng, W, Kuang, L, Perera, SMDC, Pitman, MC, Brown, MF & Liang, H 2016, 'A Usual G-Protein-Coupled Receptor in Unusual Membranes', Angewandte Chemie - International Edition, vol. 55, no. 2, pp. 588-592. https://doi.org/10.1002/anie.201508648
Chawla U, Jiang Y, Zheng W, Kuang L, Perera SMDC, Pitman MC et al. A Usual G-Protein-Coupled Receptor in Unusual Membranes. Angewandte Chemie - International Edition. 2016 Jan 11;55(2):588-592. https://doi.org/10.1002/anie.201508648
Chawla, Udeep ; Jiang, Yunjiang ; Zheng, Wan ; Kuang, Liangju ; Perera, Suchithranga M D C ; Pitman, Michael C. ; Brown, Michael F ; Liang, Hongjun. / A Usual G-Protein-Coupled Receptor in Unusual Membranes. In: Angewandte Chemie - International Edition. 2016 ; Vol. 55, No. 2. pp. 588-592.
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