Supplementary Figure 7: Location of ADPKD-associated missense variants in PC2 and PC1.

(a) PC2 tetramer shown looking onto TOP domain, from the side and a pore domain/VSLD sliced view. Positions of missense variant sites are highlighted by spheres colored according to the predicted impact of a mutation on the channel structure as indicated in Supplementary Table 1 (low – yellow; high – magenta). Variant sites cluster in the TOP domain and around the top of the pore. Fewer variants lie in the VSLD. (b) ADPKD-associated missense variants of PC1 mapped to a model of PC1 channel-like domain derived from the PC2 structure. It is unclear whether PC1 forms a homotetramer or a heterotetramer with PC2 or other polycystins. As with PC2, missense variants in PC1 cluster in the TOP domain. (c) PC2 variant sites mapped on to either a PC2 monomer cartoon representation (left panel) or molecular surface representation. Only a small percentage of the missense variant sites are exposed on the protein surface with the rest buried. The most closely packed cluster maps to the TOP domain TLC extension arm that participates in TOP-TOP interaction (Gly318/Cys331/Tyr345/Thr448).