Cryo-EM structure of TRPV5. (A and B) Side (A) and top (B) views of nanodisc-reconstituted TRPV5 1–660 at 2.9-Å resolution, with the subunits colored individually. The nanodisc density surrounds the transmembrane region of the channel (white). (C and D) Side (C) and top (D) views of the TRPV5 tetrameric complex, using the same subunit colors as in A and B. (E) Side view of a TRPV5 monomer with the functional domains colored individually. Structural elements are depicted as ribbons for α-helices, arrows for β-sheets, and ropes for unordered loops. (F) Domain organization of TRPV5, with domains colored as in E. The dashed line denotes a region that was not resolved in the structure but is present in the full-length channel.