Article
- The EMBO Journal (2005) 24, 1111 - 1121
- doi:10.1038/sj.emboj.7600610
Published online: 10 March 2005
Subject Categories:
Structure and biochemical analysis of a secretin pilot protein
Paula I Lario1, Richard A Pfuetzner1, Elizabeth A Frey1, Louise Creagh2, Charles Haynes2, Anthony T Maurelli3 and Natalie C J Strynadka1
- Department of Biochemistry, University of British Columbia, Vancouver, BC, Canada
- Biotechnology Laboratory, University of British Columbia, Vancouver, BC, Canada
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Correspondence to:
Natalie C J Strynadka, Department of Biochemistry & Molecular Biology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3. Tel.: +1 604 822 0789; Fax: +1 604 822 5227; E-mail: natalie@byron.biochem.ubc.ca
Received 21 October 2004; Accepted 10 February 2005
Abstract
The ability to translocate virulence proteins into host cells through a type III secretion apparatus (TTSS) is a hallmark of several Gram-negative pathogens including Shigella, Salmonella, Yersinia, Pseudomonas, and enteropathogenic Escherichia coli. In common with other types of bacterial secretion apparatus, the assembly of the TTSS complex requires the preceding formation of its integral outer membrane secretin ring component. We have determined at 1.5 Å the structure of MxiM28–142, the Shigella pilot protein that is essential for the assembly and membrane association of the Shigella secretin, MxiD. This represents the first atomic structure of a secretin pilot protein from the several bacterial secretion systems containing an orthologous secretin component. A deep hydrophobic cavity is observed in the novel 'cracked barrel' structure of MxiM, providing a specific binding domain for the acyl chains of bacterial lipids, a proposal that is supported by our various lipid/MxiM complex structures. Isothermal titration analysis shows that the C-terminal domain of the secretin, MxiD525–570, hinders lipid binding to MxiM.
Keywords:
- lipid binding,
- secretin pilot,
- TTSS,
- type III secretion,
- X-ray crystallography
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