TCDB is operated by the Saier Lab Bioinformatics Group

8.A.213.  The Bon Domain-containing Protein (Bon DP) Family 

This protein plays an important role in maintaining outer membrane integrity (Bryant et al. 2020, Ranava et al. 2021). It supports proper folding and function of BamA under envelope stress conditions (Ranava et al. 2021) and binds specifically to anionic phospholipids via the BON 2 domain (Bryant et al. 2020). This interaction is essential for function and guides the protein to the cell division site. It mediates co-selection of antibiotic and heavy metal resistance in bacteria (Sun et al. 2023). It functions like an efflux pump to confer resistance to various antibiotics, especially for ceftazidime, with a >32-fold increase in minimum inhibitory concentration (MIC). The BON protein could interact with several metal ions, such as copper and silver, which have been associated with the induced co-regulation of antibiotic and heavy metal resistance in bacteria. The BON protein was shown to spontaneously self-assemble into a trimer and generate a central pore-like architecture for antibiotic transport. A WXG motif as a molecular switch is essential for forming the transmembrane oligomeric pores and controls the interaction between the BON protein and the cell membrane. A mechanism termed "one-in, one-out", was proposed. The present study provides new insights into the structure and function of BON protein and a previously unidentified resistance mechanism (Sun et al. 2023).

References associated with 8.A.213 family:

Bryant, J.A., F.C. Morris, T.J. Knowles, R. Maderbocus, E. Heinz, G. Boelter, D. Alodaini, A. Colyer, P.J. Wotherspoon, K.A. Staunton, M. Jeeves, D.F. Browning, Y.R. Sevastsyanovich, T.J. Wells, A.E. Rossiter, V.N. Bavro, P. Sridhar, D.G. Ward, Z.S. Chong, E.C. Goodall, C. Icke, A.C. Teo, S.S. Chng, D.I. Roper, T. Lithgow, A.F. Cunningham, M. Banzhaf, M. Overduin, and I.R. Henderson. (2020). Structure of dual BON-domain protein DolP identifies phospholipid binding as a new mechanism for protein localisation. Elife 9:. 33315009
Ranava, D., Y. Yang, L. Orenday-Tapia, F. Rousset, C. Turlan, V. Morales, L. Cui, C. Moulin, C. Froment, G. Munoz, J. Rech, J. Marcoux, A. Caumont-Sarcos, C. Albenne, D. Bikard, and R. Ieva. (2021). Lipoprotein DolP supports proper folding of BamA in the bacterial outer membrane promoting fitness upon envelope stress. Elife 10:. 33847565
Sun, S., M. Wang, J. Xiang, Y. Shao, L. Li, R.A. Sedjoah, G. Wu, J. Zhou, and Z. Xin. (2023). BON domain-containing protein-mediated co-selection of antibiotic and heavy metal resistance in bacteria. Int J Biol Macromol 238: 124062. [Epub: Ahead of Print] 36933600