| Structural highlights
Disease
[TRPC3_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.
Function
[TRPC3_HUMAN] Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C, and by inositol 1,4,5-triphosphate receptors (ITPR) with bound IP3. May also be activated by internal calcium store depletion.[1] [2] [3] [4]
Publication Abstract from PubMed
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.
Structure of the human lipid-gated cation channel TRPC3.,Fan C, Choi W, Sun W, Du J, Lu W Elife. 2018 May 4;7. pii: 36852. doi: 10.7554/eLife.36852. PMID:29726814[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Woo JS, Hwang JH, Ko JK, Weisleder N, Kim DH, Ma J, Lee EH. S165F mutation of junctophilin 2 affects Ca2+ signalling in skeletal muscle. Biochem J. 2010 Mar 15;427(1):125-34. doi: 10.1042/BJ20091225. PMID:20095964 doi:http://dx.doi.org/10.1042/BJ20091225
- ↑ Zhu X, Jiang M, Peyton M, Boulay G, Hurst R, Stefani E, Birnbaumer L. trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry. Cell. 1996 May 31;85(5):661-71. PMID:8646775
- ↑ Zhu X, Jiang M, Birnbaumer L. Receptor-activated Ca2+ influx via human Trp3 stably expressed in human embryonic kidney (HEK)293 cells. Evidence for a non-capacitative Ca2+ entry. J Biol Chem. 1998 Jan 2;273(1):133-42. PMID:9417057
- ↑ Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G. Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature. 1999 Jan 21;397(6716):259-63. doi: 10.1038/16711. PMID:9930701 doi:http://dx.doi.org/10.1038/16711
- ↑ Fan C, Choi W, Sun W, Du J, Lu W. Structure of the human lipid-gated cation channel TRPC3. Elife. 2018 May 4;7. pii: 36852. doi: 10.7554/eLife.36852. PMID:29726814 doi:http://dx.doi.org/10.7554/eLife.36852
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