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 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

doi:10.1038/ncomms10140

Ternary structure reveals mechanism of a membrane diacylglycerol kinase

Journal Article · Thu Dec 17 00:00:00 EST 2015 · Nature Communications

DOI:https://doi.org/10.1038/ncomms10140· OSTI ID:1233178

Li, Dianfan ^[1]; Stansfeld, Phillip J. ^[2]; Sansom, Mark S. P. ^[2]; Keogh, Aaron ^[1]; Vogeley, Lutz ^[1]; Howe, Nicole ^[1]; Lyons, Joseph A. ^[1]; Aragao, David ^[1]; Fromme, Petra ^[3]; Fromme, Raimund ^[3]; Basu, Shibom ^[3]; Grotjohann, Ingo ^[3]; Kupitz, Christopher ^[3]; Rendek, Kimberley ^[3]; Weierstall, Uwe ^[3]; Zatsepin, Nadia A. ^[3]; Cherezov, Vadim ^[4]; Liu, Wei ^[3]; Bandaru, Sateesh ^[5]; English, Niall J. ^[5] more »

Trinity College Dublin, Dublin (Ireland)
Univ. of Oxford, Oxford (United Kingdom)
Arizona State Univ., Tempe, AZ (United States)
Univ. of Southern California, Los Angeles, CA (United States)
Univ. College Dublin, Dublin (Ireland)
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Univ. of Hamburg, Hamburg (Germany)
Univ. of Konstanz, Konstanz (Germany)
SLAC National Accelerator Lab., Menlo Park, CA (United States)

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.

View Accepted Manuscript (DOE)

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

Alternate ID(s):: OSTI ID: 1233322

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 6; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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