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Molecular structure of an open human K_ATP channel.

ABSTRACT: K_ATP channels are metabolic sensors that translate intracellular ATP/ADP balance into membrane excitability. The molecular composition of K_ATP includes an inward-rectifier potassium channel (Kir) and an ABC transporter-like sulfonylurea receptor (SUR). Although structures of K_ATP have been determined in many conformations, in all cases, the pore in Kir is closed. Here, we describe human pancreatic K_ATP (hK_ATP) 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_ATP exhibits the unique (among inward-rectifier channels) property of PIP₂-independent opening, which appears to be correlated with a docked cytoplasmic domain in the absence of PIP₂.

SUBMITTER: Zhao C

PROVIDER: S-EPMC8640745 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Molecular structure of an open human KATP channel.

Zhao Chen C MacKinnon Roderick R

Proceedings of the National Academy of Sciences of the United States of America 20211101 48

KATP channels are metabolic sensors that translate intracellular ATP/ADP balance into membrane excitability. The molecular composition of KATP includes an inward-rectifier potassium channel (Kir) and an ABC transporter-like sulfonylurea receptor (SUR). Although structures of KATP have been determined in many conformations, in all cases, the pore in Kir is closed. Here, we describe human pancreatic KATP (hKATP) structures with an open pore at ...[more]

PMID: 34815345

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