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. This study provides new insights into the structure and function of BON protein and a previously unidentified resistance mechanism (Sun et al. 2023). This is elaborated by Sun and Chen 2024 who discussed the role of BON domain-containing proteins in antibiotic resistance.
References:
The Bon domain-containing protein, DolP, of 191 aas and one N-terminal TMS. 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 minimal 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. This study provides new insights into the structure and function of BON proteins and a previously unidentified resistance mechanism (Sun et al. 2023).
Bon domain protein, DolP, of Escherichia coli K12
Molecular chaparone, OsmY, of 201 aas and 1 N-terminal TMS.
OsmY of E. coli K12
BON domain-containing protein of 208 aas and 1 N-terminal TMS.
BON domain protein of Rhodospirillaceae bacterium (marine metagenome)
BON domain-containing protein of 270 aas and 1 N-terminal TMS.
BON domain protein of Rheinheimera sp. MM224
Phospholipid-binding protein of 192 aas and 1 N-terminal TMS.
PL-BP of Candidatus Pelagibacter sp. (marine metagenome)
BON domain-containing protein of 213 aas and 2 TMSs, one N-terminal and one near the C-terminus.
BON domain protein of Magnetovibrio sp. (subsurface metagenome)