Fig. 6: Structural basis of RhoA-dependent gating of TRPV4.
From: TRPV4-Rho GTPase complex structures reveal mechanisms of gating and disease
a Side-by-side comparison of cryo-EM densities of RhoA in closed (cyan), ligand-free (green), and open (pink) states at thresholding 0.25. 4 Å low-pass filter and the same B-factor (−50) are applied to all cryo-EM maps. b Root-mean-square-fluctuation (RMSF) of residues in the TRPV4 ARD in GSK101-TRPV4, GSK101-TRPV4-RhoA, GSK279-TRPV4, and GSK279-TRPV4-RhoA systems from all-atom MD simulations. In the GSK279-bound state, RhoA binding significantly reduced ARD fluctuation. Shades indicate standard deviations from 12 replicas. c–e Comparison of closed, ligand-free, and open structures viewed from the intracellular side (c) Close-up view of the ARD (d) and coupling domain (e HTHCD, TRP, and S2–S3). Arrows indicate movements of the ARD. ARD/CD rigid-body movement occurs at an individual protomer level. f Ligand-dependent channel gating of TRPV4-RhoA. Schematic illustration of the conformational rearrangements in the S6 gate, ARD, and RhoA during TRPV4 gating.
