Figure 4

Simulation of PIP2 docking to the pre-S1 domain. (A, top) Ribbon diagram of TRPC6 (PDB: 6UZ833). The pre-S1 domain is depicted in red. (Bottom) Surface plot of the pre-S1 shoulder. (B) Surface representations of the arrangement of the short PIP2 chain and the pre-S1 domain/shoulder with the linker segment between the ARD and pre-S1. (C) Trace showing the current through the double mutants R437Q/R746Q channel upon the activation of VSP. Gray dashed line indicates zero current level. (D) Summary of C429S and R437Q/R746Q kinetics to VSP activation for comparison with TRPC6WT and R437Q (n = 5 and n = 4 for C429S and R437Q/R746Q, respectively). *p < 0.05 or **p < 0.01.