Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli. Nature 2011 Feb 24;470(7335):558-62
Date
02/26/2011Pubmed ID
21350490Pubmed Central ID
PMC3078058DOI
10.1038/nature09743Scopus ID
2-s2.0-79952145187 (requires institutional sign-in at Scopus site) 167 CitationsAbstract
Gram-negative bacteria, such as Escherichia coli, expel toxic chemicals through tripartite efflux pumps that span both the inner and outer membrane. The three parts are an inner membrane, substrate-binding transporter; a membrane fusion protein; and an outer-membrane-anchored channel. The fusion protein connects the transporter to the channel within the periplasmic space. A crystallographic model of this tripartite efflux complex has been unavailable because co-crystallization of the various components of the system has proven to be extremely difficult. We previously described the crystal structures of both the inner membrane transporter CusA and the membrane fusion protein CusB of the CusCBA efflux system of E. coli. Here we report the co-crystal structure of the CusBA efflux complex, showing that the transporter (or pump) CusA, which is present as a trimer, interacts with six CusB protomers and that the periplasmic domain of CusA is involved in these interactions. The six CusB molecules seem to form a continuous channel. The affinity of the CusA and CusB interaction was found to be in the micromolar range. Finally, we have predicted a three-dimensional structure for the trimeric CusC outer membrane channel and developed a model of the tripartite efflux assemblage. This CusC(3)-CusB(6)-CusA(3) model shows a 750-kilodalton efflux complex that spans the entire bacterial cell envelope and exports Cu I and Ag I ions.
Author List
Su CC, Long F, Zimmermann MT, Rajashankar KR, Jernigan RL, Yu EWAuthor
Michael T. Zimmermann PhD Director, Assistant Professor in the Clinical and Translational Science Institute department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
CopperCrystallization
Crystallography, X-Ray
Escherichia coli
Escherichia coli Proteins
Membrane Transport Proteins
Metals, Heavy
Models, Molecular
Multiprotein Complexes
Protein Binding
Protein Multimerization
Protein Structure, Quaternary
Protein Structure, Tertiary
Silver
Static Electricity