Allosteric activation of plasma membrane receptors--physiological implications and structural origins.
Allosteric modulation of receptors has physiological not just pharmacological significance. Thus, the chemical context in which an agonist signal is received can have a major impact on the nature of the physiological response by modifying receptor sensitivity and/or maximal activity-even the nature of the signalling response. In addition, recognising that an endogenous activator is the allosteric modulator of a known receptor, rather than the agonist of a novel receptor, has the potential to solve, in dramatic fashion, key physiological questions. What is an allosteric modulator and why are allosteric effects on receptors so diverse and frequently complex? What is the scope of allosteric effects? Can the existence of endogenous modulators be predicted from a receptor's amino acid sequence? How should screening for endogenous allosteric modulators be undertaken? These questions form the framework of this mini-review on physiological and structural aspects of receptor allostery.
Conigrave
Arthur D
AD
School of Molecular and Microbial Biosciences, University of Sydney, NSW 2006, Australia. a.conigrave@biochem.usyd.edu.au
Franks
Alison H
AH
D000494:Allosteric Regulation; D000495:Allosteric Site / Q000502:physiology; D001667:Binding, Competitive; D002462:Cell Membrane / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D004798:Enzymes / Q000502:physiology*; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D004798:Enzymes; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate