Structural basis of G protein-coupled receptor function.
The vast majority of extracellular signaling molecules, like hormones and neurotransmitters, interact with a class of membranous receptors characterized by a uniform molecular architecture of seven transmembrane alpha-helices linked by extra- and intracelluar peptide loops. In a reversible manner, binding of diverse agonists to heptahelical receptors leads to activation of a limited repertoire of heterotrimeric guanine nucleotide-binding proteins (G proteins) forwarding the signal to intracellular effectors such as enzymes and ion channels. Proper functioning of a G protein-coupled receptor is based on a complex interplay of structural determinants which are ultimately responsible for receptor folding, trafficking and transmembrane signaling. Applying novel biochemical and molecular biological methods interesting insights into receptor structure/function relationships became available. These studies have a significant impact on our understanding of the molecular basis of human diseases and may eventually lead to novel therapeutic strategies.
Institut für Pharmakologie, Freie Universität Berlin, Germany. schoberg@zedat.fu-berlin.de
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D000818:Animals; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins