Description
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. The active site architecture shows clear evidence of having arisen by convergent evolution.
Details
Title
- Ternary structure reveals mechanism of a membrane diacylglycerol kinase
Contributors
- Li, Dianfan (Author)
- Stansfeld, Phillip J. (Author)
- Sansom, Mark S. P. (Author)
- Keogh, Aaron (Author)
- Vogeley, Lutz (Author)
- Howe, Nicole (Author)
- Lyons, Joseph A. (Author)
- Aragao, David (Author)
- Fromme, Petra (Author)
- Fromme, Raimund (Author)
- Basu, Shibom (Author)
- Grotjohann, Ingo (Author)
- Kupitz, Christopher (Author)
- Rendek, Kimberley (Author)
- Weierstall, Uwe (Author)
- Zatsepin, Nadia (Author)
- Cherezov, Vadim (Author)
- Liu, Wei (Author)
- Bandaru, Sateesh (Author)
- English, Niall J. (Author)
- Gati, Cornelius (Author)
- Barty, Anton (Author)
- Yefanov, Oleksandr (Author)
- Chapman, Henry N. (Author)
- Diederichs, Kay (Author)
- Messerschmidt, Marc (Author)
- Boutet, Sebastien (Author)
- Williams, Garth J. (Author)
- Seibert, M. Marvin (Author)
- Caffrey, Martin (Author)
- College of Liberal Arts and Sciences (Contributor)
- School of Molecular Sciences (Contributor)
- Biodesign Institute (Contributor)
- Applied Structural Discovery (Contributor)
- Department of Physics (Contributor)
Date Created
The date the item was original created (prior to any relationship with the ASU Digital Repositories.)
2015-12-17
Resource Type
Collections this item is in
Identifier
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Digital object identifier: 10.1038/ncomms10140
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Identifier TypeInternational standard serial numberIdentifier Value2041-1723
Note
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The final version of this article, as published in Nature Communications, can be viewed online at: https://www.nature.com/articles/ncomms10140
Citation and reuse
Cite this item
This is a suggested citation. Consult the appropriate style guide for specific citation guidelines.
Li, D., Stansfeld, P. J., Sansom, M. S., Keogh, A., Vogeley, L., Howe, N., . . . Caffrey, M. (2015). Ternary structure reveals mechanism of a membrane diacylglycerol kinase. Nature Communications, 6, 10140. doi:10.1038/ncomms10140