G protein-coupled receptor activation: analysis of a highly constrained, "straitjacketed" rhodopsin.
G protein-coupled receptor (GPCR) activation is generally assumed to result in a significant structural rearrangement of the receptor, presumably involving the rigid body movement of transmembrane helices. We have investigated the activation of the GPCR rhodopsin by the construction and analysis of a mutant which contains a total of four disulfide bonds connecting the cytoplasmic ends of helices 1 and 7, and 3 and 5, and the extracellular ends of helices 3 and 4, and 5 and 6. Despite the constraints imposed by four disulfides, this "straitjacketed" receptor retains the ability to activate the G protein transducin and, therefore, provides insight into the molecular mechanism of the initial step in signal transduction of this important class of receptors.
Struthers
M
M
Department of Biochemistry and Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454, USA.
Yu
H
H
Oprian
D D
DD
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D011956:Receptors, Cell Surface; D012243:Rhodopsin; D019204:GTP-Binding Proteins