| Structural highlights6e1k is a 6 chain structure with sequence from Arath and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | |
| Gene: | TPC1, CCH1, FOU2, At4g03560, F9H3.19, T5L23.5 (ARATH) |
| Experimental data: | Check | | Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function[TPC1_ARATH] Functions as a voltage-gated inward-rectifying Ca(2+) channel (VDCC) across the vacuole membrane. Is one of the essential components of the slow vacuolar (SV) channel. Acts as the major ROS-responsive Ca(2+) channel and is the possible target of Al-dependent inhibition. Involved in the regulation of germination and stomatal movement.[1] [2]
Publication Abstract from PubMed
Voltage-sensing domains (VSDs) couple changes in transmembrane electrical potential to conformational changes that regulate ion conductance through a central channel. Positively charged amino acids inside each sensor cooperatively respond to changes in voltage. Our previous structure of a TPC1 channel captured an example of a resting-state VSD in an intact ion channel. To generate an activated-state VSD in the same channel we removed the luminal inhibitory Ca(2+)-binding site (Cai(2+)), which shifts voltage-dependent opening to more negative voltage and activation at 0 mV. Cryo-EM reveals two coexisting structures of the VSD, an intermediate state 1 that partially closes access to the cytoplasmic side but remains occluded on the luminal side and an intermediate activated state 2 in which the cytoplasmic solvent access to the gating charges closes, while luminal access partially opens. Activation can be thought of as moving a hydrophobic insulating region of the VSD from the external side to an alternate grouping on the internal side. This effectively moves the gating charges from the inside potential to that of the outside. Activation also requires binding of Ca(2+) to a cytoplasmic site (Caa(2+)). An X-ray structure with Caa(2+) removed and a near-atomic resolution cryo-EM structure with Cai(2+) removed define how dramatic conformational changes in the cytoplasmic domains may communicate with the VSD during activation. Together four structures provide a basis for understanding the voltage-dependent transition from resting to activated state, the tuning of VSD by thermodynamic stability, and this channel's requirement of cytoplasmic Ca(2+) ions for activation.
Structural basis for activation of voltage sensor domains in an ion channel TPC1.,Kintzer AF, Green EM, Dominik PK, Bridges M, Armache JP, Deneka D, Kim SS, Hubbell W, Kossiakoff AA, Cheng Y, Stroud RM Proc Natl Acad Sci U S A. 2018 Sep 6. pii: 1805651115. doi:, 10.1073/pnas.1805651115. PMID:30190435[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See AlsoReferences
- ↑ Kawano T, Kadono T, Fumoto K, Lapeyrie F, Kuse M, Isobe M, Furuichi T, Muto S. Aluminum as a specific inhibitor of plant TPC1 Ca2+ channels. Biochem Biophys Res Commun. 2004 Nov 5;324(1):40-5. PMID:15464979 doi:http://dx.doi.org/S0006-291X(04)02051-0
- ↑ Peiter E, Maathuis FJ, Mills LN, Knight H, Pelloux J, Hetherington AM, Sanders D. The vacuolar Ca2+-activated channel TPC1 regulates germination and stomatal movement. Nature. 2005 Mar 17;434(7031):404-8. PMID:15772667 doi:http://dx.doi.org/nature03381
- ↑ Kintzer AF, Green EM, Dominik PK, Bridges M, Armache JP, Deneka D, Kim SS, Hubbell W, Kossiakoff AA, Cheng Y, Stroud RM. Structural basis for activation of voltage sensor domains in an ion channel TPC1. Proc Natl Acad Sci U S A. 2018 Sep 6. pii: 1805651115. doi:, 10.1073/pnas.1805651115. PMID:30190435 doi:http://dx.doi.org/10.1073/pnas.1805651115
|