| Title: | Comparison of class A and D G protein-coupled receptors: common features in structure and activation |
| Author(s): | Eilers M; Hornak V; Smith SO; Konopka JB; |
| Address: | "Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York 11794-5222, USA" |
| ISSN/ISBN: | 0006-2960 (Print) 0006-2960 (Linking) |
| Abstract: | "All G protein-coupled receptors (GPCRs) share a common seven TM helix architecture and the ability to activate heterotrimeric G proteins. Nevertheless, these receptors have widely divergent sequences with no significant homology. We present a detailed structure-function comparison of the very divergent Class A and D receptors to address whether there is a common activation mechanism across the GPCR superfamily. The Class A and D receptors are represented by the vertebrate visual pigment rhodopsin and the yeast alpha-factor pheromone receptor Ste2, respectively. Conserved amino acids within each specific receptor class and amino acids where mutation alters receptor function were located in the structures of rhodopsin and Ste2 to assess whether there are functionally equivalent positions or regions within these receptors. We find several general similarities that are quite striking. First, strongly polar amino acids mediate helix interactions. Their mutation generally leads to loss of function or constitutive activity. Second, small and weakly polar amino acids facilitate tight helix packing. Third, proline is essential at similar positions in transmembrane helices 6 and 7 of both receptors. Mapping the specific location of the conserved amino acids and sites of constitutively active mutations identified conserved microdomains on transmembrane helices H3, H6, and H7, suggesting that there are underlying similarities in the mechanism of the widely divergent Class A and Class D receptors" |
| Keywords: | "Amino Acid Sequence Conserved Sequence Crystallography, X-Ray Fungal Proteins/chemistry/metabolism Hydrogen Bonding Hydrophobic and Hydrophilic Interactions Models, Molecular Molecular Sequence Data Protein Structure, Secondary Receptors, G-Protein-Couple;" |
| Notes: | "MedlineEilers, Markus Hornak, Viktor Smith, Steven O Konopka, James B eng R01 GM041412/GM/NIGMS NIH HHS/ R01 GM055107/GM/NIGMS NIH HHS/ GM-41412/GM/NIGMS NIH HHS/ GM55107/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. 2005/06/22 Biochemistry. 2005 Jun 28; 44(25):8959-75. doi: 10.1021/bi047316u" |
