title: Interaction mediated by the putative tip regions of MdsA and MdsC in the formation of a Salmonella-specific tripartite efflux pump.
abstract: To survive in the presence of a wide range of toxic compounds, gram-negative bacteria expel such compounds via tripartite efflux pumps that span both the inner and outer membranes. The Salmonella-specific MdsAB pump consists of MdsB, a resistance-nodulation-division (RND)-type inner membrane transporter (IMT) that requires the membrane fusion protein (MFP) MdsA, and an outer membrane protein (OMP; MdsC or TolC) to form a tripartite efflux complex. In this study, we investigated the role of the putative tip regions of MdsA and its OMPs, MdsC and TolC, in the formation of a functional MdsAB-mediated efflux pump. Comparative analysis indicated that although sequence homologies of MdsA and MdsC with other MFPs and OMPs, respectively, are extremely low, key residues in the putative tip regions of these proteins are well conserved. Mutagenesis studies on these conserved sites demonstrated their importance for the physical and functional interactions required to form an MdsAB-mediated pump. Our studies suggest that, despite differences in the primary amino acid sequences and functions of various OMPs and MFPs, interactions mediated by the conserved tip regions of OMP and MFP are required for the formation of functional tripartite efflux pumps in gram-negative bacteria.
authors: Department of Life Science, Chung-Ang University, Seoul, Republic of Korea.
authors: Saemee
authors: S
authors: Song
authors: Department of Life Science, Chung-Ang University, Seoul, Republic of Korea.
authors: Soonhye
authors: S
authors: Hwang
authors: Department of Life Science, Chung-Ang University, Seoul, Republic of Korea.
authors: Seunghwa
authors: S
authors: Lee
authors: Department of Food and Animal Biotechnology, Department of Agricultural Biotechnology, Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Nam-Chul
authors: NC
authors: Ha
authors: Department of Life Science, Chung-Ang University, Seoul, Republic of Korea.
authors: Kangseok
authors: K
authors: Lee
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D050576:Membrane Fusion Proteins / Q000737:chemistry* / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D012486:Salmonella typhimurium / Q000378:metabolism*; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D050576:Membrane Fusion Proteins; D026901:Membrane Transport Proteins