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TitleStructure and gating mechanism of the transient receptor potential channel TRPV3.
Journal, issue, pagesNat Struct Mol Biol, Vol. 25, Issue 9, Page 805-813, Year 2018
Publish dateAug 20, 2018
AuthorsAppu K Singh / Luke L McGoldrick / Alexander I Sobolevsky /
PubMed AbstractTransient receptor potential vanilloid subfamily member 3 (TRPV3) channel plays a crucial role in skin physiology and pathophysiology. Mutations in TRPV3 are associated with various skin diseases, ...Transient receptor potential vanilloid subfamily member 3 (TRPV3) channel plays a crucial role in skin physiology and pathophysiology. Mutations in TRPV3 are associated with various skin diseases, including Olmsted syndrome, atopic dermatitis, and rosacea. Here we present the cryo-electron microscopy structures of full-length mouse TRPV3 in the closed apo and agonist-bound open states. The agonist binds three allosteric sites distal to the pore. Channel opening is accompanied by conformational changes in both the outer pore and the intracellular gate. The gate is formed by the pore-lining S6 helices that undergo local α-to-π helical transitions, elongate, rotate, and splay apart in the open state. In the closed state, the shorter S6 segments are entirely α-helical, expose their nonpolar surfaces to the pore, and hydrophobically seal the ion permeation pathway. These findings further illuminate TRP channel activation and can aid in the design of drugs for the treatment of inflammatory skin conditions, itch, and pain.
External linksNat Struct Mol Biol / PubMed:30127359 / PubMed Central
MethodsEM (single particle)
Resolution4.0 - 6.5 Å
Structure data

8919

6dvw

EMDB-8919, PDB-6dvw:
Cryo-EM structure of mouse TRPV3
Method: EM (single particle) / Resolution: 4.3 Å

8920

6dvy

EMDB-8920, PDB-6dvy:
Cryo-EM structure of mouse TRPV3 in complex with 2-Aminoethoxydiphenyl borate (2-APB)
Method: EM (single particle) / Resolution: 4.0 Å

8921

6dvz

EMDB-8921, PDB-6dvz:
Cryo-EM structure of mouse TRPV3-Y564A in complex with 2-Aminoethoxydiphenyl borate (2-APB)
Method: EM (single particle) / Resolution: 4.24 Å

EMDB-8925:
Cryo-EM structure of mouse TRPV3-Y564A
Method: EM (single particle) / Resolution: 6.5 Å

Chemicals

ChemComp-FZ4:
2-aminoethyl diphenylborinate

Source
  • Homo sapiens (human)
  • mus musculus (house mouse)
KeywordsMEMBRANE PROTEIN / TRPV3 / TRP channels / Calcium channels

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