Ternary structure reveals mechanism of a membrane diacylglycerol kinase

Dianfan Li, Phillip J. Stansfeld, Mark S P Sansom, Aaron Keogh, Lutz Vogeley, Nicole Howe, Joseph A. Lyons, David Aragao, Petra Fromme, Raimund Fromme, Shibom Basu, Ingo Grotjohann, Christopher Kupitz, Kimberley Rendek, Uwe Weierstall, Nadia Zatsepin, Vadim Cherezov, Wei Liu, Sateesh Bandaru, Niall J. EnglishCornelius Gati, Anton Barty, Oleksandr Yefanov, Henry N. Chapman, Kay Diederichs, Marc Messerschmidt, Sébastien Boutet, Garth J. Williams, M. Marvin Seibert, Martin Caffrey

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 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 (US)
Article number10140
JournalNature Communications
Volume6
DOIs
StatePublished - Dec 17 2015

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Diacylglycerol Kinase
adenosine triphosphate
Adenosine Triphosphate
membranes
Membranes
Catalytic Domain
Lipids
lipids
Mutagenesis
Phosphatidic Acids
Diglycerides
Substrates
Cell membranes
analogs
mutagenesis
Hydroxyl Radical
Cytosol
Escherichia coli
Phosphotransferases
Escherichia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Li, D., Stansfeld, P. J., Sansom, M. S. P., Keogh, A., Vogeley, L., Howe, N., ... Caffrey, M. (2015). Ternary structure reveals mechanism of a membrane diacylglycerol kinase. Nature Communications, 6, [10140]. https://doi.org/10.1038/ncomms10140

Ternary structure reveals mechanism of a membrane diacylglycerol kinase. / 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; 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.; Seibert, M. Marvin; Caffrey, Martin.

In: Nature Communications, Vol. 6, 10140, 17.12.2015.

Research output: Contribution to journalArticle

Li, D, Stansfeld, PJ, Sansom, MSP, Keogh, A, Vogeley, L, Howe, N, Lyons, JA, Aragao, D, Fromme, P, Fromme, R, Basu, S, Grotjohann, I, Kupitz, C, Rendek, K, Weierstall, U, Zatsepin, N, Cherezov, V, Liu, W, Bandaru, S, English, NJ, Gati, C, Barty, A, Yefanov, O, Chapman, HN, Diederichs, K, Messerschmidt, M, Boutet, S, Williams, GJ, Seibert, MM & Caffrey, M 2015, 'Ternary structure reveals mechanism of a membrane diacylglycerol kinase', Nature Communications, vol. 6, 10140. https://doi.org/10.1038/ncomms10140
Li D, Stansfeld PJ, Sansom MSP, Keogh A, Vogeley L, Howe N et al. Ternary structure reveals mechanism of a membrane diacylglycerol kinase. Nature Communications. 2015 Dec 17;6. 10140. https://doi.org/10.1038/ncomms10140
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 ; 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. ; Seibert, M. Marvin ; Caffrey, Martin. / Ternary structure reveals mechanism of a membrane diacylglycerol kinase. In: Nature Communications. 2015 ; Vol. 6.
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