Linked Life Data

15251227

Source:http://linkedlifedata.com/resource/pubmed/id/15251227

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-7-14
pubmed:abstractText
The superfamily of G-protein-coupled receptors (GPCRs) could be subclassified into 7 families (A, B, large N-terminal family B-7 transmembrane helix, C, Frizzled/Smoothened, taste 2, and vomeronasal 1 receptors) among mammalian species. Cloning and functional studies of GPCRs have revealed that the superfamily of GPCRs comprises receptors for chemically diverse native ligands including (1) endogenous compounds like amines, peptides, and Wnt proteins (i.e., secreted proteins activating Frizzled receptors); (2) endogenous cell surface adhesion molecules; and (3) photons and exogenous compounds like odorants. The combined use of site-directed mutagenesis and molecular modeling approaches have provided detailed insight into molecular mechanisms of ligand binding, receptor folding, receptor activation, G-protein coupling, and regulation of GPCRs. The vast majority of family A, B, C, vomeronasal 1, and taste 2 receptors are able to transduce signals into cells through G-protein coupling. However, G-protein-independent signaling mechanisms have also been reported for many GPCRs. Specific interaction motifs in the intracellular parts of these receptors allow them to interact with scaffold proteins. Protein engineering techniques have provided information on molecular mechanisms of GPCR-accessory protein, GPCR-GPCR, and GPCR-scaffold protein interactions. Site-directed mutagenesis and molecular dynamics simulations have revealed that the inactive state conformations are stabilized by specific interhelical and intrahelical salt bridge interactions and hydrophobic-type interactions. Constitutively activating mutations or agonist binding disrupts such constraining interactions leading to receptor conformations that associates with and activate G-proteins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0163-7258
pubmed:author
pubmed:issnType
Print
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21-80
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Molecular mechanisms of ligand binding, signaling, and regulation within the superfamily of G-protein-coupled receptors: molecular modeling and mutagenesis approaches to receptor structure and function.
pubmed:affiliation
Department of Pharmacology, Institute of Medical Biology, University of Tromsø, N-9037 Tromsø, Norway. kurt.k@fagmed.uit.no
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't