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TitleStructure of the human lipid-gated cation channel TRPC3.
Journal, issue, pagesElife, Vol. 7, Year 2018
Publish dateMay 4, 2018
AuthorsChen Fan / Wooyoung Choi / Weinan Sun / Juan Du / Wei Lü /
PubMed AbstractThe 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 ...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.
External linksElife / PubMed:29726814 / PubMed Central
MethodsEM (single particle)
Resolution3.3 Å
Structure data

EMDB-7620, PDB-6cud:
Structure of the human TRPC3 in a lipid-occupied, closed state
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-6OE:
(2S)-3-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-2-(hexanoyloxy)propyl hexanoate

ChemComp-FGJ:
(2R)-3-hydroxypropane-1,2-diyl dihexanoate

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Canonical transient receptor potential 3 (TRPC3) lipid-sensitive non-selective cation channel

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