Publication Date:
2008-09-27
Description:
Opsin, the ligand-free form of the G-protein-coupled receptor rhodopsin, at low pH adopts a conformationally distinct, active G-protein-binding state known as Ops*. A synthetic peptide derived from the main binding site of the heterotrimeric G protein-the carboxy terminus of the alpha-subunit (GalphaCT)-stabilizes Ops*. Here we present the 3.2 A crystal structure of the bovine Ops*-GalphaCT peptide complex. GalphaCT binds to a site in opsin that is opened by an outward tilt of transmembrane helix (TM) 6, a pairing of TM5 and TM6, and a restructured TM7-helix 8 kink. Contacts along the inner surface of TM5 and TM6 induce an alpha-helical conformation in GalphaCT with a C-terminal reverse turn. Main-chain carbonyl groups in the reverse turn constitute the centre of a hydrogen-bonded network, which links the two receptor regions containing the conserved E(D)RY and NPxxY(x)(5,6)F motifs. On the basis of the Ops*-GalphaCT structure and known conformational changes in Galpha, we discuss signal transfer from the receptor to the G protein nucleotide-binding site.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scheerer, Patrick -- Park, Jung Hee -- Hildebrand, Peter W -- Kim, Yong Ju -- Krauss, Norbert -- Choe, Hui-Woog -- Hofmann, Klaus Peter -- Ernst, Oliver P -- England -- Nature. 2008 Sep 25;455(7212):497-502. doi: 10.1038/nature07330.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Medizinische Physik und Biophysik (CC2), Charite - Universitatsmedizin Berlin, Chariteplatz 1, D-10117 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18818650" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Motifs
;
Animals
;
Arginine/chemistry/metabolism
;
Binding Sites
;
Cattle
;
Conserved Sequence
;
Crystallization
;
Crystallography, X-Ray
;
GTP-Binding Protein alpha Subunits/*chemistry/*metabolism
;
Models, Biological
;
Models, Molecular
;
Protein Conformation
;
Regeneration
;
Retinaldehyde/chemistry/metabolism
;
Rhodopsin/chemistry
;
Rod Opsins/*chemistry/*metabolism
;
Signal Transduction
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
