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TitleVoltage-gating and cytosolic Ca activation mechanisms of two-pore channel AtTPC1.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 118, Issue 49, Year 2021
Publish dateDec 7, 2021
AuthorsFan Ye / Lingyi Xu / Xiaoxiao Li / Weizhong Zeng / Ninghai Gan / Cheng Zhao / Wei Yang / Youxing Jiang / Jiangtao Guo /
PubMed Abstract two-pore channel AtTPC1 is a voltage-gated, Ca-modulated, nonselective cation channel that is localized in the vacuolar membrane and responsible for generating slow vacuolar (SV) current. Under ... two-pore channel AtTPC1 is a voltage-gated, Ca-modulated, nonselective cation channel that is localized in the vacuolar membrane and responsible for generating slow vacuolar (SV) current. Under depolarizing membrane potential, cytosolic Ca activates AtTPC1 by binding at the EF-hand domain, whereas luminal Ca inhibits the channel by stabilizing the voltage-sensing domain II (VSDII) in the resting state. Here, we present 2.8 to 3.3 Å cryoelectron microscopy (cryo-EM) structures of AtTPC1 in two conformations, one in closed conformation with unbound EF-hand domain and resting VSDII and the other in a partially open conformation with Ca-bound EF-hand domain and activated VSDII. Structural comparison between the two different conformations allows us to elucidate the structural mechanisms of voltage gating, cytosolic Ca activation, and their coupling in AtTPC1. This study also provides structural insight into the general voltage-gating mechanism among voltage-gated ion channels.
External linksProc Natl Acad Sci U S A / PubMed:34845029 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.3 Å
Structure data

31585

7fhk

EMDB-31585, PDB-7fhk:
Structure of AtTPC1 with 1 mM Ca2+
Method: EM (single particle) / Resolution: 3.3 Å

31586

7fhl

EMDB-31586, PDB-7fhl:
Structure of AtTPC1 with 50 mM Ca2+
Method: EM (single particle) / Resolution: 3.1 Å

31587

7fhn

EMDB-31587, PDB-7fhn:
Structure of AtTPC1 D240A/D454A/E528A mutant with 1 mM Ca2+
Method: EM (single particle) / Resolution: 3.3 Å

31588

7fho

EMDB-31588, PDB-7fho:
Structure of AtTPC1 D240A/D454A/E528A mutant with 50 mM Ca2+
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-CA:
Unknown entry

Source
  • arabidopsis thaliana (thale cress)
  • human respiratory syncytial virus
KeywordsTRANSPORT PROTEIN / non-selective cation channel / dimer / vacuole

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