The Hv1 proton channel is evidently unique among voltage sensor domain proteins in mediating an intrinsic 'aqueous' H+ conductance (GAQ). Mutation of a highly conserved 'gating charge' residue in the S4 helix (R1H) confers a resting-state H+ 'shuttle' conductance (GSH) in VGCs and Ci VSP, and we now report that R1H is sufficient to reconstitute GSH in Hv1 without abrogating GAQ. Second-site mut...

Meirhaeghe et al. recently showed that the T allele of a C vs T exchange at position 825 of the gene encoding for the beta3 subunit of heterotrimeric G proteins (GNB3) is associated with enhanced coronary constriction after intracoronary administration of methylergonovine. The 825T allele has also been shown to be associated with an enhanced response after activation of G protein coupled recept...

Enhanced G protein activation has been implicated to underlie the increased sodium-proton transport in blood cells, an impaired characteristic observed in 30% to 50% of patients with essential hypertension. Recently, significant association between a C825T polymorphism of the gene encoding the G protein beta3 subunit and hypertension was demonstrated in a white population, together with the fin...

Activation of GPCRs (G-protein-coupled receptors) leads to conformational changes that ultimately initiate signal transduction. Activated GPCRs transiently combine with and activate heterotrimeric G-proteins resulting in GTP replacement of GDP on the G-protein alpha subunit. Both the detailed structural changes essential for productive GDP/GTP exchange on the G-protein alpha subunit and the str...

RGS (regulator of G protein signaling) proteins containing the G protein -like (GGL) domain (RGS6, RGS7, RGS9, and RGS11) interact with the fifth member of the G protein -subunit family, G 5. This interaction is necessary for the stability of both the RGS protein and for G 5. Consistent with this notion, we have found that elevation of RGS9-1 mRNA levels by transgene expression does not increas...

G-proteins (guanine nucleotide-binding proteins) are membrane-attached proteins composed of three subunits, alpha, beta, and gamma. They transduce signals from G-protein coupled receptors (GPCRs) to target effector proteins. The agonistactivated receptor induces a conformational change in the G-protein trimer so that the alpha-subunit binds GTP in exchange for GDP and alpha-GTP, and betagamma-s...