Campus Units

Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of, Chemistry, Bioinformatics and Computational Biology, Physics and Astronomy

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

2011

Journal or Book Title

Nature

Volume

470

Issue

7335

First Page

558

Last Page

562

DOI

10.1038/nature09743

Abstract

Gram-negative bacteria, such as Escherichia coli, expel toxic chemicals via tripartite efflux pumps spanning both the inner and outer membranes. The three parts are: 1) a membrane fusion protein connecting 2) a substrate-binding inner membrane transporter to 3) an outer membrane-anchored channel in the periplasmic space. A crystallographic model of this tripartite efflux complex has been unavailable simply because co-crystallization of different components of the system has proven to be extremely difficult. We previously described the crystal structures of both the inner membrane transporter CusA1 and membrane fusion protein CusB2 of the CusCBA efflux system3,4 from E. coli. We here report the co-crystal structure of the CusBA efflux complex, revealing the trimeric CusA efflux pump interacts with six CusB protomers at the upper half of the periplasmic domain. These six CusB molecules form a channel extending contiguously from the top of the pump. The affinity of the CusA and CusB interaction was found to be in the micromolar range. Finally, we predicted a three-dimensional structure of the trimeric CusC outer membrane channel, and develop a model of the tripartite efflux assemblage. This CusC3-CusB6-CusA3 model presents a 750 kDa efflux complex spanning the entire bacterial cell envelope to export Cu(I)/Ag(I) ions.

Comments

This is a manuscript of an article published as Su, Chih-Chia, Feng Long, Michael T. Zimmermann, Kanagalaghatta R. Rajashankar, Robert L. Jernigan, and Edward W. Yu. "Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli." Nature 470, no. 7335 (2011): 558. doi: 10.1038/nature09743. Posted with permission.

Copyright Owner

Macmillan Publishers Limited

Language

en

File Format

application/pdf