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TitleConformational ensemble of the human TRPV3 ion channel.
Journal, issue, pagesNat Commun, Vol. 9, Issue 1, Page 4773, Year 2018
Publish dateNov 14, 2018
AuthorsLejla Zubcevic / Mark A Herzik / Mengyu Wu / William F Borschel / Marscha Hirschi / Albert S Song / Gabriel C Lander / Seok-Yong Lee /
PubMed AbstractTransient 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 ...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.
External linksNat Commun / PubMed:30429472 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 4.0 Å
Structure data

9115

6mho

EMDB-9115, PDB-6mho:
Structure of the human TRPV3 channel in the apo conformation
Method: EM (single particle) / Resolution: 3.4 Å

9117

6mhs

EMDB-9117, PDB-6mhs:
Structure of the human TRPV3 channel in a putative sensitized conformation
Method: EM (single particle) / Resolution: 3.2 Å

9119

6mhv

EMDB-9119, PDB-6mhv:
Structure of human TRPV3 in the presence of 2-APB in C4 symmetry
Method: EM (single particle) / Resolution: 3.5 Å

9120

6mhw

EMDB-9120, PDB-6mhw:
Structure of human TRPV3 in the presence of 2-APB in C2 symmetry (1)
Method: EM (single particle) / Resolution: 4.0 Å

9121

6mhx

EMDB-9121, PDB-6mhx:
Structure of human TRPV3 in the presence of 2-APB in C2 symmetry (2)
Method: EM (single particle) / Resolution: 4.0 Å

Source
  • homo sapiens (human)
KeywordsTRANSPORT PROTEIN / membrane protein / ion channel / TRP channel / calcium transport

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