Structure of the human lipid-gated cation channel TRPC3
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 me...
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doaj-5ae732c45d3c4b2bb0d50981c27d9c462021-05-05T15:50:32ZengeLife Sciences Publications LtdeLife2050-084X2018-05-01710.7554/eLife.36852Structure of the human lipid-gated cation channel TRPC3Chen Fan0Wooyoung Choi1Weinan Sun2Juan Du3Wei Lü4https://orcid.org/0000-0002-3009-1025Van Andel Institute, Grand Rapids, United StatesVan Andel Institute, Grand Rapids, United StatesVollum Institute, Portland, United StatesVan Andel Institute, Grand Rapids, United StatesVan Andel Institute, Grand Rapids, United StatesThe 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.https://elifesciences.org/articles/36852cryo-EMion channellipid-sensitive |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chen Fan Wooyoung Choi Weinan Sun Juan Du Wei Lü |
spellingShingle |
Chen Fan Wooyoung Choi Weinan Sun Juan Du Wei Lü Structure of the human lipid-gated cation channel TRPC3 eLife cryo-EM ion channel lipid-sensitive |
author_facet |
Chen Fan Wooyoung Choi Weinan Sun Juan Du Wei Lü |
author_sort |
Chen Fan |
title |
Structure of the human lipid-gated cation channel TRPC3 |
title_short |
Structure of the human lipid-gated cation channel TRPC3 |
title_full |
Structure of the human lipid-gated cation channel TRPC3 |
title_fullStr |
Structure of the human lipid-gated cation channel TRPC3 |
title_full_unstemmed |
Structure of the human lipid-gated cation channel TRPC3 |
title_sort |
structure of the human lipid-gated cation channel trpc3 |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2018-05-01 |
description |
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. |
topic |
cryo-EM ion channel lipid-sensitive |
url |
https://elifesciences.org/articles/36852 |
work_keys_str_mv |
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