(a) Cartoon representation of the TRP helix, pre-S1 elbow, TMD, and linker domain, showing their interaction. Lipid 1 is shown in sticks. W673 on the TRP helix stacks with P553 and G552 forming a hydrogen bond with the backbone oxygen (dashed line) of P546 on the S4-S5 linker. The side chain of R677 is in close contact with the head group of lipid 1. (b–e) The pore lining helix S6 and the TRP helix in TRPC3 (b), TRPV1 (c), TRPA1 (d), and TRPM4 (e). The angle between the S6 and TRP helices are indicated; only two subunits are shown for clarity. The hinge connecting the S6 and TRP helix is highlighted in red. (f–h) Comparison of TRPC3 with TRPV1, TRPA1, and TRPM4, respectively, focusing on the S4, S5 and TRP helix. Structures are superimposed using backbone atoms in S4 and S5. TRPC3 is in blue, whereas TRPV1, TRPA1 and TRPM4 are in red. Proteins are shown in ribbon representation, and lipid 1 in TRPC3 is shown in sticks. Arrows indicate the relative movement of the TRP helix in TRPC3 compared to TRPV1, TRPA1 or TRPM4.