1. Biophysics and Structural Biology
  2. Neuroscience
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Molecular structure of human KATP in complex with ATP and ADP

  1. Kenneth Pak Kin Lee
  2. Jue Chen Is a corresponding author
  3. Roderick MacKinnon Is a corresponding author
  1. The Rockefeller University, United States
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Cite as: eLife 2017;6:e32481 doi: 10.7554/eLife.32481

Abstract

In many excitable cells KATP channels respond to intracellular adenosine nucleotides: ATP inhibits while ADP activates. We present two structures of the human pancreatic KATP channel, containing the ABC transporter SUR1 and the inward-rectifier K+ channel Kir6.2, in the presence of Mg2+ and nucleotides. These structures, referred to as quatrefoil and propeller forms, were determined by single-particle cryo-EM at 3.9 Å and 5.6 Å, respectively. In both forms ATP occupies the inhibitory site in Kir6.2. The nucleotide-binding domains of SUR1 are dimerized with Mg2+-ATP in the degenerate site and Mg2+-ADP in the consensus site. A lasso extension forms an interface between SUR1 and Kir6.2 adjacent to the ATP site in the propeller form, and is disrupted in the quatrefoil form. These structures support the role of SUR1 as an ADP sensor and highlight the lasso extension as a key regulatory element in ADP's ability to override ATP inhibition.

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Author details

  1. Kenneth Pak Kin Lee

    Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jue Chen

    Laboratory of Membrane Biology and Biophysics, The Rockefeller University, New York, United States
    For correspondence
    juechen@rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-2075-4283
  3. Roderick MacKinnon

    Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, New York, United States
    For correspondence
    mackinn@rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0001-7605-4679

Funding

Human Frontier Science Program

  • Kenneth Pak Kin Lee

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Kenton J Swartz, Reviewing Editor, National Institutes of Health, United States

Publication history

  1. Received: October 3, 2017
  2. Accepted: December 29, 2017
  3. Accepted Manuscript published: December 29, 2017 (version 1)

Copyright

© 2017, Lee et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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