Structure-activity relationships of G protein-coupled receptors.
The primary function of cell-surface receptors is to discriminate the specific signaling molecule or ligand from a large array of chemically diverse extracellular substances and to activate an effector signaling cascade that triggers an intracellular response and eventually a biological effect. G protein-coupled cell-surface receptors (GPCRs) mediate their intracellular actions through the activation of guanine nucleotide-binding signal-transducing proteins (G proteins), which form a diverse family of regulatory GTPases that, in the GTP-bound state, bind and activate downstream membrane-localized effectors. Hundreds of GPCRs signal through one or more of these G proteins in response to a large variety of stimuli including photons, neurotransmitters, and hormones of variable molecular structure. The mechanisms by which these ligands provoke activation of the receptor/G-protein system are highly complex and multifactorial. Knowledge and mapping of the structural determinants and requirements for optimal GPCR function are of paramount importance, not only for a better and more detailed understanding of the molecular basis of ligand action and receptor function in normal and abnormal conditions, but also for a rational design of early diagnostic and therapeutic tools that may allow exogenous regulation of receptor and G protein function in disease processes.
Ulloa-Aguirre
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Unidad de Investigación en Medicina Reproductiva, Hospital de Gineco Obstetricia Luis Castelazo Ayala, Instituto Mexicano del Seguro Social, México, D.F., Mexico. aulloaa@buzon.main.conacyt.mx
Stanislaus
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Janovick
J A
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Conn
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D000818:Animals; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D013329:Structure-Activity Relationship
D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins