Crystal structure of the SOS cell division inhibitor SulA and in complex with FtsZ.
SulA halts cell division in Escherichia coli by binding to the major component of the division machinery FtsZ. We have solved the crystal structure of SulA alone and in complex with FtsZ from Pseudomonas aeruginosa. SulA is expressed when the SOS response is induced. This is a mechanism to inhibit cell division and repair DNA in the event of DNA damage. FtsZ is a tubulin-like protein that forms polymers, with the active-site GTPase split across two monomers. One monomer provides the GTP-binding site and the other, through its T7 loop nucleotide hydrolysis. Our structures show that SulA is a dimer, and that SulA inhibits cell division neither by binding the nucleotide-binding site nor by inducing conformational changes in FtsZ. Instead, SulA binds the T7 loop surface of FtsZ, opposite the nucleotide-binding site, blocking polymer formation. These findings explain why GTP hydrolysis and polymer turnover are required for SulA inhibition.
Cordell
Suzanne C
SC
Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom.
Robinson
Elva J H
EJ
Lowe
Jan
J
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D002455:Cell Division; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins; D019281:Dimerization; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; D029968:Escherichia coli Proteins; C071525:FtsZ protein, Bacteria; C053139:sulA protein, E coli; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases