Ternary structure reveals mechanism of a membrane diacylglycerol kinase

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Dianfan Li, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences Chinese Academy of Sciences
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  • Phillip J. Stansfeld, University of Oxford, Oxford
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  • Mark S P Sansom, University of Oxford, Oxford
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  • Aaron Keogh, Trinity College Dublin
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  • Lutz Vogeley, Trinity College Dublin
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  • Nicole Howe, Trinity College Dublin
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  • Joseph A. Lyons
  • David Aragao, Australian Synchrotron
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  • Petra Fromme, Arizona State University
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  • Raimund Fromme, Arizona State University
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  • Shibom Basu, Arizona State University
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  • Ingo Grotjohann, Arizona State University
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  • Christopher Kupitz, Arizona State University
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  • Kimberley Rendek, Arizona State University
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  • Uwe Weierstall, Arizona State University
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  • Nadia A. Zatsepin, Arizona State University
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  • Vadim Cherezov, University of Southern California
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  • Wei Liu, Arizona State University
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  • Sateesh Bandaru, University College Dublin, Dublin
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  • Niall J. English, University College Dublin, Dublin
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  • Cornelius Gati, Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron DESY
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  • Anton Barty, Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron DESY
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  • Oleksandr Yefanov, Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron DESY
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  • Henry N. Chapman, Universitat Hamburg
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  • Kay Diederichs, Universität Konstanz
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  • Marc Messerschmidt, BioXFEL Science and Technology Center
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  • Sébastien Boutet, Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory
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  • Garth J. Williams, Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory
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  • M. Marvin Seibert, Uppsala universitet
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  • Martin Caffrey, Trinity College Dublin

Diacylglycerol kinase catalyses the ATP-dependent conversion of diacylglycerol to phosphatidic acid in the plasma membrane of Escherichia coli. The small size of this integral membrane trimer, which has 121 residues per subunit, means that available protein must be used economically to craft three catalytic and substrate-binding sites centred about the membrane/cytosol interface. How nature has accomplished this extraordinary feat is revealed here in a crystal structure of the kinase captured as a ternary complex with bound lipid substrate and an ATP analogue. Residues, identified as essential for activity by mutagenesis, decorate the active site and are rationalized by the ternary structure. The 3-phosphate of the ATP analogue is positioned for direct transfer to the primary hydroxyl of the lipid whose acyl chain is in the membrane. A catalytic mechanism for this unique enzyme is proposed. The active site architecture shows clear evidence of having arisen by convergent evolution.

Original languageEnglish
Article number10140
JournalNature Communications
Volume6
ISSN2041-1723
DOIs
Publication statusPublished - 2015

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