Article info Vol. 7  No. 1   pp.  6 ~ 11
Title Assembly model of the heavy metal efflux pump CusBAC based on the protein-protein interaction
Authors Seokho Hong1, Jin-Sik Kim1,2, Inseong Jo1, So-Young Jun3 and Nam-Chul Ha1,*
Institutions 1Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Center for Food and Bioconvergence, Center for Food Safety and Toxicology, Seoul National University, Seoul 08826, Republic of Korea, 2Current address: Unit on Structural and Chemical Biology of Membrane Proteins, Cell Biology and Neurobiology Branch, National Institute of Child Health and Human Development, National Institutes of Health, 35A Convent Drive, Bethesda, MD 20892, USA, 3College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea *Correspondence: hanc210@snu.ac.kr
Abstract The CusBAC heavy metal efflux pump of Escherichia coli consists of three essential components spanning the inner membrane, periplasmic space, and outer membrane. The periplasmic adaptor protein CusB connects the inner membrane transporter CusA to the outer membrane factor CusC. The structural studies revealed that the periplasmic component CusB has a unique structure in the CusC interaction region. Recent advances in cryo-electron microscopy have revealed the intermeshing cogwheel interaction between the periplasmic adaptor protein and the outer membrane factor in other types of tripartite efflux pumps, such as AcrAB-TolC and MacAB-TolC. In this study, we built a model of the full complex of the CusBAC pump, where the inner α-helices in CusB are twisted inward to make a similar cogwheel structure to that of AcrA. Binding assay results support the finding that the CusB and CusC binding mode is shared with AcrA and TolC in AcrAB-TolC. Our results give structural insight into a common mechanism for how to seal these proteins to prevent leaks in tripartite efflux pumps.