Supplementary Figure 5: PC2 fold, topology and VSLD structure.
From: Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2)
Comparison of the monomer structure for (a) PC2; (b) TRPV1 (PDB: 3J5P) and (c) VGIC CavAb (PDB: 4MVO) viewed in the plane of the membrane (dotted line). Domains are colored according to domain (as Fig. 2a). The N-terminal Ankyrin repeat domain (ARD) of TRPV1 is colored grey. (d) Superposition of monomer structures of PC2 (cyan), TRPV1 (purple) and CavAb (yellow). The structures were superposed with the SSM matching routine in COOT using the S5-S6 pore domain of PC2 tetramer as a reference (to avoid bias from the differently positioned VSLDs). All 3 structures show similar relative orientations of the pore and VSDs. (e) Two perpendicular views of the VSLD (S1-S4). A cluster of conserved residues at the cytosolic end of the four-helix bundle are show in stick form. The conserved lysine residues on S4 (Lys572, Lys575) are in close proximity to a series of buried negatively charged residues. The sidechains of residues that could not be resolved in the EM maps (due to radiation damage/flexibility) have been modelled for illustrative purposes. (f) Comparison of the location of positively charged residues on PC2’s S4 VSLD helix (light blue) with the S4 voltage sensor helix of NavAb / CavAb (yellow, PDB: 4MVO) which contains four arginines (R1-R4). (g) Superposition of the individual VSLD for PC2, TRPV1 and CavAb (colored as in (d)).
