Abstract:
:Heterotrimeric G proteins function as molecular relays that mediate signal transduction from heptahelical receptors in the cell membrane to intracellular effector proteins. Crystallographic studies have demonstrated that guanine nucleotide exchange on the Galpha subunit causes specific conformational changes in three key "switch" regions of the protein, which regulate binding to Gbetagamma subunits, receptors, and effector proteins. In the present study, nitroxide side chains were introduced at sites within the switch I region of Galphai to explore the structure and dynamics of this region throughout the G protein cycle. EPR spectra obtained for each of the Galpha(GDP), Galpha(GDP)betagamma heterotrimer and Galpha(GTPgammaS) conformations are consistent with the local environment observed in the corresponding crystal structures. Binding of the heterotrimer to activated rhodopsin to form the nucleotide-free (empty) complex, for which there is no crystal structure, causes prominent changes relative to the heterotrimer in the structure of switch I and contiguous sequences. The data identify a putative pathway of allosteric changes triggered by receptor binding and, together with previously published data, suggest elements of a mechanism for receptor-catalyzed nucleotide exchange.
journal_name
Proc Natl Acad Sci U S Aauthors
Oldham WM,Van Eps N,Preininger AM,Hubbell WL,Hamm HEdoi
10.1073/pnas.0702623104subject
Has Abstractpub_date
2007-05-08 00:00:00pages
7927-32issue
19eissn
0027-8424issn
1091-6490pii
0702623104journal_volume
104pub_type
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