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Structure paper

TitleMolecular structure of an open human K channel.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 118, Issue 48, Year 2021
Publish dateNov 30, 2021
AuthorsChen Zhao / Roderick MacKinnon /
PubMed AbstractK channels are metabolic sensors that translate intracellular ATP/ADP balance into membrane excitability. The molecular composition of K includes an inward-rectifier potassium channel (Kir) and an ...K channels are metabolic sensors that translate intracellular ATP/ADP balance into membrane excitability. The molecular composition of K includes an inward-rectifier potassium channel (Kir) and an ABC transporter-like sulfonylurea receptor (SUR). Although structures of K have been determined in many conformations, in all cases, the pore in Kir is closed. Here, we describe human pancreatic K (hK) structures with an open pore at 3.1- to 4.0-Å resolution using single-particle cryo-electron microscopy (cryo-EM). Pore opening is associated with coordinated structural changes within the ATP-binding site and the channel gate in Kir. Conformational changes in SUR are also observed, resulting in an area reduction of contact surfaces between SUR and Kir. We also observe that pancreatic hK exhibits the unique (among inward-rectifier channels) property of PIP-independent opening, which appears to be correlated with a docked cytoplasmic domain in the absence of PIP.
External linksProc Natl Acad Sci U S A / PubMed:34815345 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 4 Å
Structure data

EMDB-24839, PDB-7s5t:
Human KATP channel in open conformation, focused on Kir (C166S G334D double mutant) and SUR TMD0
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-24840, PDB-7s5v:
Human KATP channel in open conformation, focused on SUR
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-24842, PDB-7s5x:
Human KATP channel in open conformation, focused on Kir and one SUR, position 1
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-24843, PDB-7s5y:
Human KATP channel in open conformation, focused on Kir and one SUR, position 2
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-24844, PDB-7s5z:
Human KATP channel in open conformation, focused on Kir and one SUR, position 3
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-24845, PDB-7s60:
Human KATP channel in open conformation, focused on Kir and one SUR, position 4
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-24846, PDB-7s61:
Human KATP channel in open conformation, focused on Kir and one SUR, position 5
Method: EM (single particle) / Resolution: 4 Å

Chemicals

ChemComp-K:
Unknown entry

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

ChemComp-MG:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / ion channel / KATP / ATP-sensitive potassium channel

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