Protons stabilize the closed conformation of gain-of-function mutants of the TRPV1 channel

► Low pH stabilizes the closed conformations of specific activating mutations of TRPV1 ► The S1 region plays an important role in TRPV1 channel gating ► TRPV1 and potassium channels might share a similar gating mechanism involving S1 ► The S1-pore interface stabilizes conformations associated with TRPV1 gating