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Elife. 2018 May 4;7. pii: e36852. doi: 10.7554/eLife.36852.

Structure of the human lipid-gated cation channel TRPC3.

Fan C#1, Choi W#1, Sun W2, Du J1, Lu W1.

Author information

1
Van Andel Institute, Grand Rapids, United States.
2
Vollum Institute, Portland, United States.
#
Contributed equally

Abstract

The TRPC channels are crucially involved in store-operated calcium entry and calcium homeostasis, and they are implicated in human diseases such as neurodegenerative disease, cardiac hypertrophy, and spinocerebellar ataxia. We present a structure of the full-length human TRPC3, a lipid-gated TRPC member, in a lipid-occupied, closed state at 3.3 Angstrom. TRPC3 has four elbow-like membrane reentrant helices prior to the first transmembrane helix. The TRP helix is perpendicular to, and thus disengaged from, the pore-lining S6, suggesting a different gating mechanism from other TRP subfamily channels. The third transmembrane helix S3 is remarkably long, shaping a unique transmembrane domain, and constituting an extracellular domain that may serve as a sensor of external stimuli. We identified two lipid-binding sites, one being sandwiched between the pre-S1 elbow and the S4-S5 linker, and the other being close to the ion-conducting pore, where the conserved LWF motif of the TRPC family is located.

KEYWORDS:

cryo-EM; human; ion channel; lipid-sensitive; molecular biophysics; structural biology

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