Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 276, Issue 23, Pages 20160-20166Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M101599200
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- NIGMS NIH HHS [GM30355] Funding Source: Medline
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Regulator of G protein signaling (RGS) proteins must bind membranes in an orientation that permits the protein-protein interactions necessary for regulatory activity. RGS4 binds to phospholipid surfaces in a slow, multistep process that leads to maximal GTPase-activating protein (GAP) activity. When RGS4 is added to phospholipid vesicles that contain m2 or m1 muscarinic receptor and G(i), G(z), or G(q), GAP activity increases similar to3-fold over 4 h at 30 degreesC and more slowly at 20 degreesC, This increase in GAP activity is preceded by several other events that suggest that, after binding, optimal interaction with G protein and receptor requires reorientation of RGS4 on the membrane surface, a conformational change, or both. Binding of RGS4 is initially reversible but becomes irreversible within 5 min. Onset of irreversibility parallels initial quenching of tryptophan fluorescence (t(1/2) similar to 30 s), Further quenching occurs after binding has become irreversible (t(1/2) similar to 6 min) but is complete well before maximal GAP activity is attained. These processes all appear to be energetically driven by the amphipathic N-terminal domain of RGS4 and are accelerated by palmitoylation of cysteine residues in this region. The RGS4 N-terminal domain confers similar membrane binding behavior on the RGS domains of either RGS10 or RGSZ1.
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