The sporulation protein SirA inhibits the binding of DnaA to the origin of replication by contacting a patch of clustered amino acids.
Bacteria regulate the frequency and timing of DNA replication initiation by controlling the activity of the replication initiator protein DnaA. SirA is a recently discovered regulator of DnaA in Bacillus subtilis whose synthesis is turned on at the start of sporulation. Here, we demonstrate that SirA contacts DnaA at a patch of 3 residues located on the surface of domain I of the replication initiator protein, corresponding to the binding site used by two unrelated regulators of DnaA found in other bacteria. We show that the interaction of SirA with domain I inhibits the ability of DnaA to bind to the origin of replication. DnaA mutants containing amino acid substitutions of the 3 residues are functional in replication initiation but are immune to inhibition by SirA.
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Ave., Cambridge, Massachusetts 02138, USA.
Lilah
L
Rahn-Lee
Houra
H
Merrikh
Alan D
AD
Grossman
Richard
R
Losick
D019943:Amino Acid Substitution / Q000235:genetics; D001412:Bacillus subtilis / Q000235:genetics* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D004261:DNA Replication; D004269:DNA, Bacterial / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D018741:Replication Origin
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; C066312:DnaA protein, Bacteria
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