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Crystal structure of the integral membrane diacylglycerol kinase

DOI: 10.1038/nature12179 DOI Help
PMID: 23676677 PMID Help

Authors: Dianfan Li (Trinity College, Dublin) , Joseph A. Lyons (Trinity College Dublin) , Valerie Pye (Trinity College Dublin) , Lutz Vogeley (Trinity College Dublin) , David Aragao (Trinity College Dublin) , Colin P. Kenyon (CSIR) , Syed T. A. Shah (Trinity College Dublin) , Christine Doherty (Trinity College Dublin) , Margaret Aherne (University of Limerick) , Martin Caffrey (Trinity College Dublin)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature , VOL 497 (7450) , PAGES 521 - 524

State: Published (Approved)
Published: May 2013

Open Access Open Access

Abstract: Diacylglycerol kinase catalyses the ATP-dependent phosphorylation of diacylglycerol to phosphatidic acid for use in shuttling water-soluble components to membrane-derived oligosaccharide and lipopolysaccharide in the cell envelope of Gram-negative bacteria1. For half a century, this 121-residue kinase has served as a model for investigating membrane protein enzymology1, 2, 3, 4, 5, 6, folding7, 8, assembly9, 10, 11, 12 and stability1, 13. Here we present crystal structures for three functional forms of this unique and paradigmatic kinase, one of which is wild type. These reveal a homo-trimeric enzyme with three transmembrane helices and an amino-terminal amphiphilic helix per monomer. Bound lipid substrate and docked ATP identify the putative active site that is of the composite, shared site type. The crystal structures rationalize extensive biochemical and biophysical data on the enzyme. They are, however, at variance with a published solution NMR model14 in that domain swapping, a key feature of the solution form, is not observed in the crystal structures.

Journal Keywords: Bacterial; Catalytic; Cell; Crystallography; X-Ray; Diacylglycerol; Enzyme; Enzyme; Lipids; Magnesium; Membrane; Models; Molecular; Mutant; Nuclear; Biomolecular; Protein; Zinc

Subject Areas: Biology and Bio-materials

Instruments: I24-Microfocus Macromolecular Crystallography

Other Facilities: APS 23 ID