Receptor and betagamma binding sites in the alpha subunit of the retinal G protein transducin.
Transmembrane receptors for hormones, neurotransmitters, light, and odorants mediate their cellular effects by activating heterotrimeric guanine nucleotide-binding proteins (G proteins). Crystal structures have revealed contact surfaces between G protein subunits, but not the surfaces or molecular mechanism through which Galphabetagamma responds to activation by transmembrane receptors. Such a surface was identified from the results of testing 100 mutant alpha subunits of the retinal G protein transducin for their ability to interact with rhodopsin. Sites at which alanine substitutions impaired this interaction mapped to two distinct Galpha surfaces: a betagamma-binding surface and a putative receptor-interacting surface. On the basis of these results a mechanism for receptor-catalyzed exchange of guanosine diphosphate for guanosine triphosphate is proposed.
Onrust
R
R
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-0450, USA.
Herzmark
P
P
Chi
P
P
Garcia
P D
PD
Lichtarge
O
O
Kingsley
C
C
Bourne
H R
HR
D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D005459:Fluorides / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D011487:Protein Conformation; D012172:Retinaldehyde / Q000494:pharmacology; D012243:Rhodopsin / Q000378:metabolism* / Q000494:pharmacology; D012374:Rod Cell Outer Segment / Q000378:metabolism; D015293:Transducin / Q000737:chemistry* / Q000378:metabolism
D017607:Aluminum Compounds; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D012243:Rhodopsin; D015293:Transducin; D005459:Fluorides; D012172:Retinaldehyde; C032311:aluminum fluoride