2X72

CRYSTAL STRUCTURE OF THE CONSTITUTIVELY ACTIVE E113Q,D2C,D282C RHODOPSIN MUTANT WITH BOUND GALPHACT PEPTIDE.

Summary for 2X72

• Entry DOI: 10.2210/pdb2x72/pdb
• Related: 1AQG 1BOJ 1BOK 1EDS 1EDV 1EDW 1EDX 1F88 1FDF 1FQJ 1FQK 1GZM 1HZX 1JFP 1L9H 1LN6 1LVZ 1N3M 1NZS 1OV0 1OV1 1TAD 1TAG 1TND 1U19 1VQX 2I35 2I36 2I37 2J4Y
• Descriptor: RHODOPSIN, GUANINE NUCLEOTIDE-BINDING PROTEIN G(T) SUBUNIT ALPHA-1, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• Functional Keywords: signaling protein, chromophore, lipoprotein, glycoprotein, transmembrane, retinal protein, g-protein coupled receptor, sensory transduction, photoreceptor protein
• Biological source: BOS TAURUS (CATTLE); More
• Total number of polymer chains: 2
• Total formula weight: 43699.47

Authors

Standfuss, J.,Edwards, P.C.,Dantona, A.,Fransen, M.,Xie, G.,Oprian, D.D.,Schertler, G.F.X. (deposition date: 2010-02-22, release date: 2011-03-16, Last modification date: 2024-11-13)

Primary citation

Standfuss, J.,Edwards, P.C.,Dantona, A.,Fransen, M.,Xie, G.,Oprian, D.D.,Schertler, G.F.X.
The Structural Basis of Agonist Induced Activation in Constitutively Active Rhodopsin
Nature, 471:656-, 2011

PubMed Abstract: G-protein-coupled receptors (GPCRs) comprise the largest family of membrane proteins in the human genome and mediate cellular responses to an extensive array of hormones, neurotransmitters and sensory stimuli. Although some crystal structures have been determined for GPCRs, most are for modified forms, showing little basal activity, and are bound to inverse agonists or antagonists. Consequently, these structures correspond to receptors in their inactive states. The visual pigment rhodopsin is the only GPCR for which structures exist that are thought to be in the active state. However, these structures are for the apoprotein, or opsin, form that does not contain the agonist all-trans retinal. Here we present a crystal structure at a resolution of 3 Å for the constitutively active rhodopsin mutant Glu 113 Gln in complex with a peptide derived from the carboxy terminus of the α-subunit of the G protein transducin. The protein is in an active conformation that retains retinal in the binding pocket after photoactivation. Comparison with the structure of ground-state rhodopsin suggests how translocation of the retinal β-ionone ring leads to a rotation of transmembrane helix 6, which is the critical conformational change on activation. A key feature of this conformational change is a reorganization of water-mediated hydrogen-bond networks between the retinal-binding pocket and three of the most conserved GPCR sequence motifs. We thus show how an agonist ligand can activate its GPCR.

PubMed: 21389983
DOI: 10.1038/NATURE09795

Experimental method

X-RAY DIFFRACTION (3 Å)