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Mitochondrial uncoupling protein 2 structure determined by NMR molecular fragment searching

Author

Listed:
  • Marcelo J. Berardi

    (Jack and Eileen Connors Structural Biology Laboratory, Harvard Medical School
    Harvard Medical School)

  • William M. Shih

    (Harvard Medical School
    Dana-Farber Cancer Institute
    Wyss Institute for Biologically Inspired Engineering, Harvard University)

  • Stephen C. Harrison

    (Jack and Eileen Connors Structural Biology Laboratory, Harvard Medical School
    Harvard Medical School
    Howard Hughes Medical Institute, Harvard Medical School)

  • James J. Chou

    (Jack and Eileen Connors Structural Biology Laboratory, Harvard Medical School
    Harvard Medical School)

Abstract

Mitochondrial proton transport The transport of small molecules across the inner mitochondrial membrane is catalysed by a large family of membrane proteins called mitochondrial carriers. More than 40 different carriers have so far been identified to selectively translocate different substrates, but only one crystal structure is available — that of the bovine ADP/ATP carrier (ANT1). Now the structure of mitochondrial uncoupling protein 2 (UCP2), a member of the carrier family that translocates protons across the mitochondrial inner membrane, has been determined using a solution nuclear magnetic resonance (NMR) method. Its overall structure of resembles that of ANT1 — despite their low sequence identity — but the matrix side of the channel is substantially more open in UCP2. This method overcomes some of the challenges associated with using NMR spectroscopy to determine the structure of membrane proteins, so it seems likely that it will be possible to use the approach to solve the high-resolution NMR structures of other membrane proteins of comparable size.

Suggested Citation

  • Marcelo J. Berardi & William M. Shih & Stephen C. Harrison & James J. Chou, 2011. "Mitochondrial uncoupling protein 2 structure determined by NMR molecular fragment searching," Nature, Nature, vol. 476(7358), pages 109-113, August.
  • Handle: RePEc:nat:nature:v:476:y:2011:i:7358:d:10.1038_nature10257
    DOI: 10.1038/nature10257
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    Cited by:

    1. Robert Dobosz & Jan Mućko & Ryszard Gawinecki, 2020. "Using Chou’s 5-Step Rule to Evaluate the Stability of Tautomers: Susceptibility of 2-[(Phenylimino)-methyl]-cyclohexane-1,3-diones to Tautomerization Based on the Calculated Gibbs Free Energies," Energies, MDPI, vol. 13(1), pages 1-14, January.
    2. Antoine Gagelin & Corentin Largeau & Sandrine Masscheleyn & Mathilde S. Piel & Daniel Calderón-Mora & Frédéric Bouillaud & Jérôme Hénin & Bruno Miroux, 2023. "Molecular determinants of inhibition of UCP1-mediated respiratory uncoupling," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Bi-Qing Li & Le-Le Hu & Lei Chen & Kai-Yan Feng & Yu-Dong Cai & Kuo-Chen Chou, 2012. "Prediction of Protein Domain with mRMR Feature Selection and Analysis," PLOS ONE, Public Library of Science, vol. 7(6), pages 1-14, June.

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