title: Crystal structure of the N-terminal ankyrin repeat domain of TRPV3 reveals unique conformation of finger 3 loop critical for channel function.
abstract: In all six members of TRPV channel subfamily, there is an ankyrin repeat domain (ARD) in their intracellular N-termini. Ankyrin (ANK) repeat, a common motif with typically 33 residues in each repeat, is primarily involved in protein-protein interactions. Despite the sequence similarity among the ARDs of TRPV channels, the structure of TRPV3-ARD, however, remains unknown. Here, we report the crystal structure of TRPV3-ARD solved at 1.95 Å resolution, which reveals six-ankyrin repeats. While overall structure of TRPV3-ARD is similar to ARDs from other members of TRPV subfamily; it, however, features a noticeable finger 3 loop that bends over and is stabilized by a network of hydrogen bonds and hydrophobic packing, instead of being flexible as seen in known TRPV-ARD structures. Electrophysiological recordings demonstrated that mutating key residues R225, R226, Q255, and F249 of finger 3 loop altered the channel activities and pharmacology. Taken all together, our findings show that TRPV3-ARD with characteristic finger 3 loop likely plays an important role in channel function and pharmacology.
authors.affiliation: Department of Neurobiology, Neuroscience Research Institute, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Di-Jing
authors.initials: DJ
authors.lastname: Shi
authors.forename: Sheng
authors.initials: S
authors.lastname: Ye
authors.forename: Xu
authors.initials: X
authors.lastname: Cao
authors.forename: Rongguang
authors.initials: R
authors.lastname: Zhang
authors.forename: KeWei
authors.initials: K
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D017089:Ankyrin Repeat; D018360:Crystallography, X-Ray; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D050916:TRPV Cation Channels / Q000737:chemistry* / Q000502:physiology
chemical_list: D050916:TRPV Cation Channels; C459445:TRPV3 protein, human