Fig. 4: Distinct intersubunit interactions in TRPC5 and TRPC1/C5.
From: Molecular architecture of the human TRPC1/C5 heteromeric channel
a, b Electrostatic charge representation of the pore entrance region of TRPC1/C5 heteromer (a) and TRPC5 homomer (b), calculated in ChimeraX56 (scale in kcal mol−1e−1). The TRPC1/C5 heteromer includes neutral Q578, which corresponds to positively charged K560 in the equivalent region of TRPC5. c Cryo-EM structure of the TRPC1/C5 heteromer, with dotted boxes (left) and a schematic structure (right) highlighting intersubunit junctions expanded in (d–i). d Close-up of the S3–S5 intersubunit interface (top) and intraprotomeric region with cholesteryl hemisuccinate (CHS, yellow) comprising the S1 helix, S4–S5 linker, and pre-S1 domain (bottom) in the TRPC5 homomer. e Equivalent S3–S5 intersubunit interactions in the TRPC1/C5 heteromer, shown across Views I–IV. In View I, Y542 of TRPC5 is substituted by G562 in TRPC1, leading to a loss of electrostatic interaction. f Corresponding intraprotomeric region in the TRPC1/C5 heteromer, with lipid-like densities visualized in transparent yellow. Notably, in View II, the CHS-like density is absent. g Close-up of the helix–loop–helix (HLH) region in the TRPC5 homomer. h HLH region in the TRPC1/C5 heteromer, shown in Views I and II. In View I, the loss of loop and interaction is indicated by a dotted circle. i HLH region in the previously resolved TRPC1/C4 heteromer (PDB: 8WPL), shown in the same orientations for comparison.
