Human mutations highlight an intersubunit cation-π bond that stabilizes the closed but not open or inactivated states of TRPV channels.

ABSTRACT: An adequate response of a living cell to the ever-changing environment requires integration of numerous sensory inputs. In many cases, it can be achieved even at the level of a single receptor molecule. Polymodal transient receptor potential (TRP) channels have been shown to integrate mechanical, chemical, electric, and thermal stimuli. Inappropriate gating can lead to pathologies. Among the >60 known TRP vanilloid subfamily (V) 4 mutations that interfere with bone development are Y602C or R616Q at the S4-S5 linker. A cation-π bond between the conservative residues Y602 and R616 of neighboring subunits appears likely in many homologous channel structures in a closed state. Our experiments with TRPV4 mutants indicate that the resting-closed state remains stable while the bond is substituted

SUBMITTER: Teng J 

PROVIDER: S-EPMC6511060 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature