FtsQ interaction mutants: a way to identify new antibacterial targets

Fine-mapping the Contact Sites of the Escherichia coli Cell Division Proteins FtsB and FtsL on the FtsQ Protein*

“…An extensive in vivo study using site-specific incorporation of an unnatural photo cross-linking residue at defined positions in FtsQ allowed us to probe its interaction interfaces with FtsB and FtsL at the amino acid level. Our data do not correspond to results obtained in two-hybrid assays (11,14) and indicate a hot spot for interaction with FtsB in a conserved region around residue Ser-250 at the distal end of the ␤ domain. In addition, interactions with both FtsB and FtsL were found clustered in a membrane-proximal part of the ␣ domain.…”

“…The C-terminal regions of FtsB and FtsL are believed to interact with the C-terminal ␤ domain of FtsQ, although the exact interaction interface is unknown (21,26,27). Two-hybrid analyses indicate interaction sites with other cell division proteins within the same region (11,14,15).…”

The Soluble Periplasmic Domains of Escherichia coli Cell Division Proteins FtsQ/FtsB/FtsL Form a Trimeric Complex with Submicromolar Affinity

“…FtsQ is considered a particularly attractive target for the development of inhibitors of protein-protein interactions (PPIs) that block bacterial division (7), because of the variety of interactions of FtsQ with key cell division proteins in the relatively accessible periplasm. The low cellular abundance (8) and the lack of eukaryotic homologues contribute to the conceptual suitability of FtsQ as an antibacterial drug target (9). Moreover, FtsQ is a highly conserved protein among cell wall containing bacteria (4).…”

Essential and non‐essential interactions in interactome networks: the Escherichia coli division proteins FtsQ–FtsN interaction

“…Mutations localized in the POTRA domain resulted in a decreased ability to restore the growth of an FtsQ‐depleted strain, assigning to this domain a prevalent role in FtsQ biological effects, even though the interaction with FtsQ, FtsI and FtsN was unaffected because of the presence, on the protein, of a second interaction site. On the other hand, mutations localized in the second domain (residues 136–236) seem to not have important physiological effects (Grenga et al ., ).…”

“…Therefore, to determine the biological role of these interactions, it was necessary to study the behaviour of the FtsQ double mutants where both interaction sites were mutated because, up till now, the effects observed might be assigned to a modification of the POTRA region that results in a defect of the FtsL recruitment rather than to a loss of interaction (Grenga et al ., ). Indeed, as proposed by Robson and King (), the POTRA domain serves as a chaperone that stabilizes the unfolded or partially folded form of for its cognate divisomal partner FtsL, thereby aiding its assembly into the divisome and protecting it from degradation.…”