Dual role of interactions between membranous and soluble portions of helical membrane receptors for folding and signaling.
Dramatic advances in the understanding of the molecular mechanisms of membrane receptor activation for several prototypic members of different families of receptors have taken place during the past 2-3 years. The new structures of receptor fragments or full-length receptors in different conformations have been reviewed previously in light of the large bodies of available structure-function data. However, in this article, we will compare, among different receptor families, the emerging paradigms for conformational changes during signaling. Recent advances in the understanding of membrane-protein folding suggest that these paradigms are closely related to those that describe the folding and structural stability of membrane proteins. These relate in particular to long-range interactions not only within but also between soluble or membrane-embedded parts of proteins.
Klein-Seetharaman
Judith
J
Department of Pharmacology, University of Pittsburgh School of Medicine, Biomedical Science Tower E1058, 200 Lothrop St, Pittsburgh, PA 15261, USA. jks33@pitt.edu
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D012995:Solubility
D008565:Membrane Proteins; D011956:Receptors, Cell Surface