Structure of the periplasmic component of a bacterial drug efflux pump
- *Department of Pathology, Cambridge University, Tennis Court Road, Cambridge CB2 1QP, United Kingdom; and †Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom
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Edited by Robert M. Stroud, University of California, San Francisco, CA (received for review January 16, 2004)
Abstract
Multidrug resistance among Gram-negative bacteria is conferred by three-component membrane pumps that expel diverse antibiotics from the cell. These efflux pumps consist of an inner membrane transporter such as the AcrB proton antiporter, an outer membrane exit duct of the TolC family, and a periplasmic protein known as the adaptor. We present the x-ray structure of the MexA adaptor from the human pathogen Pseudomonas aeruginosa. The elongated molecule contains three linearly arranged subdomains; a 47-Å-long α-helical hairpin, a lipoyl domain, and a six-stranded β-barrel. In the crystal, hairpins of neighboring MexA monomers pack side-by-side to form twisted arcs. We discuss the implications of the packing of molecules within the crystal. On the basis of the structure and packing, we suggest a model for the key periplasmic interaction between the outer membrane channel and the adaptor protein in the assembled drug efflux pump.
Footnotes
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↵ ‡ To whom correspondence may be addressed. E-mail: mkh20{at}hermes.cam.ac.uk or vk103{at}mole.bio.cam.ac.uk.
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This paper was submitted directly (Track II) to the PNAS office.
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Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 1T5E).
- Copyright © 2004, The National Academy of Sciences
