Fig. 3
Comparison of the TRPC4 structure with previously solved TRP channel structures (apo state). a Side views of an mTRPC4 subunit compared with other TRP family members including human TRPM4 [PDB:6BWI]24, mouse TRPV1 [PDB:3J5P]14, human TRPA1 [PDB:3J9P]18, human PKD2/TRPP1 [PDB:5T4D]19, and mouse TRPML1 [PDB:5WPV]20. b Superimposition of TRPC4 and TRPM4. c Key pore loop disulfide bond between Cys549 and Cys554 in TRPC4 and the corresponding pore loop disulfide bond between Cys993 and Cys1011 in TRPM4 (black arrows). d Differences in the organizations of the linker (pre-S1 elbow and pre-S1 helix) between the N terminus and transmembrane domains in TRPC4 and TRPM4. e Activation of whole-cell currents by reducing agents DTT and TCEP in 293T cells overexpressing wild-type TRPC4. f The double cysteine TRPC4 mutant (C549A+C554A) is activated by englerin A but not DTT. g Single cysteine mutants, C549A or C554A, are insensitive to 100 nM englerin A and 10 mM DTT. The time course of currents measured at +80 and −80 mV and I–V relationships of the peak currents in different conditions are shown
