Conformational ensemble of the human TRPV3 ion channel.

Published online

Journal Article

Transient receptor potential vanilloid channel 3 (TRPV3), a member of the thermosensitive TRP (thermoTRPV) channels, is activated by warm temperatures and serves as a key regulator of normal skin physiology through the release of pro-inflammatory messengers. Mutations in trpv3 have been identified as the cause of the congenital skin disorder, Olmsted syndrome. Unlike other members of the thermoTRPV channel family, TRPV3 sensitizes upon repeated stimulation, yet a lack of structural information about the channel precludes a molecular-level understanding of TRPV3 sensitization and gating. Here, we present the cryo-electron microscopy structures of apo and sensitized human TRPV3, as well as several structures of TRPV3 in the presence of the common thermoTRPV agonist 2-aminoethoxydiphenyl borate (2-APB). Our results show α-to-π-helix transitions in the S6 during sensitization, and suggest a critical role for the S4-S5 linker π-helix during ligand-dependent gating.

Full Text

Duke Authors

Cited Authors

  • Zubcevic, L; Herzik, MA; Wu, M; Borschel, WF; Hirschi, M; Song, AS; Lander, GC; Lee, S-Y

Published Date

  • November 14, 2018

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 4773 -

PubMed ID

  • 30429472

Pubmed Central ID

  • 30429472

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-018-07117-w

Language

  • eng

Conference Location

  • England