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Title: Ternary structure reveals mechanism of a membrane diacylglycerol kinase

Journal Article · · Nature Communications
DOI:https://doi.org/10.1038/ncomms10140· OSTI ID:1233178
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  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)
+ Show Author Affiliations

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.

Research Organization:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC03-76SF00515
OSTI ID:
1233178
Journal Information:
Nature Communications, Vol. 6, Issue 1; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 22 works
Citation information provided by
Web of Science

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  • Herrmann, Sven; Boutet, Sébastien; Duda, Brian
  • Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, Vol. 718 https://doi.org/10.1016/j.nima.2013.01.057
journal August 2013
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Cited By (7)

In meso in situ serial X-ray crystallography of soluble and membrane proteins at cryogenic temperatures journal January 2016
Global response of diacylglycerol kinase towards substrate binding observed by 2D and 3D MAS NMR text January 2019
Global response of diacylglycerol kinase towards substrate binding observed by 2D and 3D MAS NMR journal March 2019
Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis journal January 2019
Crystal structure of undecaprenyl-pyrophosphate phosphatase and its role in peptidoglycan biosynthesis journal March 2018
Lipidic cubic phase injector is a viable crystal delivery system for time-resolved serial crystallography text January 2016
Lipidic cubic phase injector is a viable crystal delivery system for time-resolved serial crystallography text January 2016

Figures / Tables (7)

Table 1(p. 3)table Table 1
Figure 1(p. 4)figure Figure 1
Figure 2(p. 5)figure Figure 2
Figure 3(p. 6)figure Figure 3
Figure 4(p. 7)figure Figure 4
Figure 5(p. 8)figure Figure 5
Figure 6(p. 9)figure Figure 6

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