Identification of the SlmA Active Site Responsible for Blocking Bacterial Cytokinetic Ring Assembly over the Chromosome

Bacterial cells use chromosome-associated division inhibitors to help coordinate the processes of dna replication and segregation with cytokinesis. slma from escherichia coli,a member of the tetracycline repressor (tetr)-like protein family,is one example of this class of regulator. it blocks the assembly of the bacterial cytokinetic ring by interfering with the polymerization of the tubulin-like ftsz protein in a manner that is dramatically stimulated upon specific dna binding. here we used a combination of molecular genetics and biochemistry to identify the active site of slma responsible for disrupting ftsz polymerization. interestingly,this site maps to a region of slma that in the published dna-free structure is partially occluded by the dna-binding domains. in this conformation,the slma structure resembles the drug/inducer-bound conformers of other tetr-like proteins,which in the absence of inducer require an inward rotation of their dna-binding domains to bind successive major grooves on operator dna. our results are therefore consistent with a model in which dna-binding activates slma by promoting a rotational movement of the dna-binding domains that fully exposes the ftsz-binding sites. slma may thus represent a special subclass of tetr-like proteins that have adapted conformational changes normally associated with inducer sensing in order to modulate an interaction with a partner protein. in this case,the adaptation ensures that slma only blocks cytokinesis in regions of the cell occupied by the origin-proximal portion of the chromosome where slma-binding sites are enriched. © 2013 cho,bernhardt.