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Ternary structure reveals mechanism of a membrane diacylglycerol kinase

DOI: 10.1038/ncomms10140 DOI Help

Authors: Dianfan Li (Trinity College Dublin) , Phillip J. Stansfeld (University of Oxford) , Mark S. P. Sansom (University of Oxford) , Aaron Keogh (Trinity College Dublin) , Lutz Vogeley (Trinity College, Dublin) , Nicole Howe (Trinity College, Dublin) , Joseph Lyons (Trinity College Dublin) , David Aragao (Trinity College, Dublin) , Petra Fromme (Arizona State University) , Raimund Fromme (Arizona State University) , Shibom Basu (Arizona State University) , Ingo Grotjohann (Arizona State University) , Christopher Kupitz (Arizona State University) , Kimberley Rendek (Arizona State University) , Uwe Weierstall (Arizona State University) , Nadia A. Zatsepin (Arizona State University) , Vadim Cherezov (University of Southern California) , Wei Liu (Arizona State University) , Sateesh Bandaru (University College Dublin) , Niall J. English (University College Dublin) , Cornelius Gati (DESY) , Anton Barty (DESY) , Oleksandr Yefanov (DESY) , Henry N. Chapman (DESY) , Kay Diederichs (University of Konstanz) , Marc Messerschmidt (SLAC National Accelerator Laboratory) , S├ębastien Boutet (SLAC National Accelerator Laboratory) , Garth J. Williams (SLAC National Accelerator Laboratory) , M. Marvin Seibert (SLAC National Accelerator Laboratory) , Martin Caffrey (Trinity College, Dublin)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 6

State: Published (Approved)
Published: December 2015

Open Access Open Access

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 ╬│-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.

Subject Areas: Biology and Bio-materials


Instruments: I24-Microfocus Macromolecular Crystallography

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