6MHS

Structure of the human TRPV3 channel in a putative sensitized conformation

Summary for 6MHS

• Entry DOI: 10.2210/pdb6mhs/pdb
• EMDB information: 9115 9117 9119 9120 9121
• Descriptor: Transient receptor potential cation channel subfamily V member 3 (1 entity in total)
• Functional Keywords: membrane protein, ion channel, trp channel, calcium transport, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 379440.88

Authors

Zubcevic, L.,Herzik, M.A.,Wu, M.,Borschel, W.F.,Hirschi, M.,Song, A.,Lander, G.C.,Lee, S.Y. (deposition date: 2018-09-18, release date: 2018-10-03, Last modification date: 2024-03-13)

Primary citation

Zubcevic, L.,Herzik Jr., M.A.,Wu, M.,Borschel, W.F.,Hirschi, M.,Song, A.S.,Lander, G.C.,Lee, S.Y.
Conformational ensemble of the human TRPV3 ion channel.
Nat Commun, 9:4773-4773, 2018

PubMed Abstract: 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.

PubMed: 30429472
DOI: 10.1038/s41467-018-07117-w

Experimental method

ELECTRON MICROSCOPY (3.2 Å)