Fig 2. Mutation on site 579 endows tsV1’s tolerance of capsaicin.

(A) Representative whole-cell current traces of mV1 (shown in blue) and tsV1 (shown in red) elicited by capsaicin from whole-cell recording at +80 and −80 mV (left panel). Comparison of capsaicin responses of mV1 (blue line) and tsV1 (red line) overlapped with fits of a Hill equation (right panel). (B) Comparison of capsaicin responses of mV1, hV1, tsV1, plV1, and pV1 overlapped with fits of a Hill equation. (C) Responsiveness to capsaicin and 2APB by chimeric channels between mV1 and tsV1. (D) The amino acid sequence representing S3–S4 linker and S4 domain from tsV1 is aligned with the corresponding sequences from other 22 mammals’ TRPV1. (E) A zoomed-in view of capsaicin binding pocket of mV1. A representative configuration of docked capsaicin is shown (upper panel). Docking of capsaicin onto a zoomed-in view of S3–S4 linker and S4 domain of tsV1 (lower panel). (F) Concentration-response curves for tsV1 and channel single-point mutants overlapped with fits of a Hill equation. (G) Comparison of capsaicin responses of mV1 (blue solid line), mV1_T551V (gray dash line), and mV1_T551M (blue dash line) overlapped with fits of a Hill equation. The number of the tested cells is indicated. All values are given as average ± s.e.m. The underlying data of panels A, B, F, and G can be found in S1 Data. 2APB, 2-aminoethoxydiphenyl borate; hV1, human TRPV1; mV, mini volt; mV1, mouse TRPV1; plV1, platypus TRPV1; pV1, polar bear TRPV1; TRPV1, transient receptor potential vanilloid type-1; tsV1, tree shrew TRPV1