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Title: Ternary structure reveals mechanism of a membrane diacylglycerol kinase

Abstract

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 γ-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. As a result, the active site architecture shows clear evidence of having arisen by convergent evolution.

Authors:
 [1];  [2];  [2];  [1];  [1];  [1];  [1];  [1];  [3];  [3];  [3];  [3];  [3];  [3];  [3];  [3];  [4];  [3];  [5];  [5] more »;  [6];  [6];  [6];  [7];  [8];  [9];  [9];  [9];  [9];  [1] « less
+ Show Author Affiliations
  1. Trinity College Dublin, Dublin (Ireland)
  2. Univ. of Oxford, Oxford (United Kingdom)
  3. Arizona State Univ., Tempe, AZ (United States)
  4. Univ. of Southern California, Los Angeles, CA (United States)
  5. Univ. College Dublin, Dublin (Ireland)
  6. Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)
  7. Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Univ. of Hamburg, Hamburg (Germany)
  8. Univ. of Konstanz, Konstanz (Germany)
  9. SLAC National Accelerator Lab., Menlo Park, CA (United States)
Publication Date:
Research Org.:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1233178
Grant/Contract Number:  
AC03-76SF00515
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 6; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; biological sciences; biochemistry; biophysics

Citation Formats

Li, Dianfan, Stansfeld, Phillip J., Sansom, Mark S. P., Keogh, Aaron, Vogeley, Lutz, Howe, Nicole, Lyons, Joseph A., Aragao, David, Fromme, Petra, Fromme, Raimund, Basu, Shibom, Grotjohann, Ingo, Kupitz, Christopher, Rendek, Kimberley, Weierstall, Uwe, Zatsepin, Nadia A., Cherezov, Vadim, Liu, Wei, Bandaru, Sateesh, English, Niall J., Gati, Cornelius, Barty, Anton, Yefanov, Oleksandr, Chapman, Henry N., Diederichs, Kay, Messerschmidt, Marc, Boutet, Sébastien, Williams, Garth J., Marvin Seibert, M., and Caffrey, Martin. Ternary structure reveals mechanism of a membrane diacylglycerol kinase. United States: N. p., 2015. Web. https://doi.org/10.1038/ncomms10140.
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Li, Dianfan, Stansfeld, Phillip J., Sansom, Mark S. P., Keogh, Aaron, Vogeley, Lutz, Howe, Nicole, Lyons, Joseph A., Aragao, David, Fromme, Petra, Fromme, Raimund, Basu, Shibom, Grotjohann, Ingo, Kupitz, Christopher, Rendek, Kimberley, Weierstall, Uwe, Zatsepin, Nadia A., Cherezov, Vadim, Liu, Wei, Bandaru, Sateesh, English, Niall J., Gati, Cornelius, Barty, Anton, Yefanov, Oleksandr, Chapman, Henry N., Diederichs, Kay, Messerschmidt, Marc, Boutet, Sébastien, Williams, Garth J., Marvin Seibert, M., & Caffrey, Martin. Ternary structure reveals mechanism of a membrane diacylglycerol kinase. United States. https://doi.org/10.1038/ncomms10140
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Li, Dianfan, Stansfeld, Phillip J., Sansom, Mark S. P., Keogh, Aaron, Vogeley, Lutz, Howe, Nicole, Lyons, Joseph A., Aragao, David, Fromme, Petra, Fromme, Raimund, Basu, Shibom, Grotjohann, Ingo, Kupitz, Christopher, Rendek, Kimberley, Weierstall, Uwe, Zatsepin, Nadia A., Cherezov, Vadim, Liu, Wei, Bandaru, Sateesh, English, Niall J., Gati, Cornelius, Barty, Anton, Yefanov, Oleksandr, Chapman, Henry N., Diederichs, Kay, Messerschmidt, Marc, Boutet, Sébastien, Williams, Garth J., Marvin Seibert, M., and Caffrey, Martin. Thu . "Ternary structure reveals mechanism of a membrane diacylglycerol kinase". United States. https://doi.org/10.1038/ncomms10140. https://www.osti.gov/servlets/purl/1233178.
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@article{osti_1233178,
title = {Ternary structure reveals mechanism of a membrane diacylglycerol kinase},
author = {Li, Dianfan and Stansfeld, Phillip J. and Sansom, Mark S. P. and Keogh, Aaron and Vogeley, Lutz and Howe, Nicole and Lyons, Joseph A. and Aragao, David and Fromme, Petra and Fromme, Raimund and Basu, Shibom and Grotjohann, Ingo and Kupitz, Christopher and Rendek, Kimberley and Weierstall, Uwe and Zatsepin, Nadia A. and Cherezov, Vadim and Liu, Wei and Bandaru, Sateesh and English, Niall J. and Gati, Cornelius and Barty, Anton and Yefanov, Oleksandr and Chapman, Henry N. and Diederichs, Kay and Messerschmidt, Marc and Boutet, Sébastien and Williams, Garth J. and Marvin Seibert, M. and Caffrey, Martin},
abstractNote = {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 γ-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. As a result, the active site architecture shows clear evidence of having arisen by convergent evolution.},
doi = {10.1038/ncomms10140},
journal = {Nature Communications},
number = 1,
volume = 6,
place = {United States},
year = {2015},
month = {12}
}
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Cited by: 8 works
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Figures / Tables:

Table 1 Table 1: Crystallization conditions, data collection and refinement statistics.
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    Works referencing / citing this record:

    Crystal structure of undecaprenyl-pyrophosphate phosphatase and its role in peptidoglycan biosynthesis
    journal, March 2018

    Global response of diacylglycerol kinase towards substrate binding observed by 2D and 3D MAS NMR
    journal, March 2019

    In meso in situ serial X-ray crystallography of soluble and membrane proteins at cryogenic temperatures
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    Lipidic cubic phase injector is a viable crystal delivery system for time-resolved serial crystallography
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    • Nogly, Przemyslaw; Panneels, Valerie; Nelson, Garrett
    • Deutsches Elektronen-Synchrotron, DESY, Hamburg
    • DOI: 10.3204/pubdb-2016-03927
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