SMolBNet 2.0: combining genetics and NMR to dissect fundamental protein-protein interactions for complex bacterial division

• Grant number: 10/51866-0
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2011
• End date: June 30, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Frederico José Gueiros Filho
• Grantee: Frederico José Gueiros Filho
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Bacterial cell division is centrally dependent on FtsZ, a prokaryotic homolog of tubulin. FtsZ triggers division by assembling the "Z ring", a supramolecular structure made up of FtsZ polymers that surrounds the cell's periphery and functions as a scaffold for the bacterial division complex. Z ring formation is regulated by modulators, the generic name given to proteins that affect FtsZ polymerization either positively or negatively. Here, we propose a multidisciplinary approach as a way to unveil the molecular details of the interaction between FtsZ and three of its modulators: ZapA, MinC and MciZ. Genetic screens have identified FtsZ mutations that make the protein insensitive to the action of each of the three modulators. These mutations likely represent amino acid substitutions that affect FtsZ's binding site for these modiulators. In order to confirm and expand these findings, we propose the establishment of an NMR platform capable of measuring the interaction between FtsZ and its modulators, and of mapping, with atomic resolution, the contacts between these proteins. Establishing this platform will require initially the assignment of all FtsZ residues. Subsequently, this information will be used in 15N-HSQC chemical shift perturbation experiments with mixtures containing FtsZ and its modulators. A second goal of this project is solving the structure of MciZ, a 40 amino acid peptide with potent FtsZ inhibitory activity. In addition to the generation of novel information on a fundamental biological process, dissecting the structural and functional details of the interaction between FtsZ and inhibitors such as MciZ and MinC is bound to produce useful information for the rational design of bacterial cell division inhibitors. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BLASIOS, VALDIR; BISSON-FILHO, ALEXANDRE W.; CASTELLEN, PATRICIA; NOGUEIRA, MARIA LUIZA C.; BETTINI, JEFFERSON; PORTUGAL, RODRIGO V.; ZERI, ANA CAROLINA M.; GUEIROS-FILHO, FREDERICO J.. Genetic and Biochemical Characterization of the MinC-FtsZ Interaction in Bacillus subtilis. PLoS One, v. 8, n. 4, APR 5 2013. (10/51866-0)

NOGUEIRA, MARIA LUIZA C.; SFORCA, MAURICIO LUIS; CHIN, YANNI K. -Y.; MOBLI, MEHDI; HANDLER, AARON; GORBATYUK, VITALIY Y.; ROBSON, SCOTT A.; KING, GLENN F.; GUEIROS-FILHO, FREDERICO J.; DE MATTOS ZERI, ANA CAROLINA. Backbone and side chain NMR assignments of Geobacillus stearothermophilus ZapA allow identification of residues that mediate the interaction of ZapA with FtsZ. BIOMOLECULAR NMR ASSIGNMENTS, v. 9, n. 2, p. 387-391, OCT 2015. (12/15123-8, 12/24916-1, 10/51866-0)

BISSON-FILHO, ALEXANDRE W.; DISCOLA, KAREN F.; CASTELLEN, PATRICIA; BLASIOS, VALDIR; MARTINS, ALEXANDRE; SFORCA, MAURICIO L.; GARCIA, WANIUS; ZERI, ANA CAROLINA M.; ERICKSON, HAROLD P.; DESSEN, ANDREA; et al. FtsZ filament capping by MciZ, a developmental regulator of bacterial division. Proceedings of the National Academy of Sciences of the United States of America, v. 112, n. 17, p. E2130-E2138, APR 28 2015. (10/51866-0)

CASTELLEN, PATRICIA; SFORCA, MAURICIO L.; GUEIROS-FILHO, FREDERICO J.; DE MATTOS ZERI, ANA CAROLINA. Backbone and side chain NMR assignments for the N-terminal domain of the cell division regulator MinC from Bacillus subtilis. BIOMOLECULAR NMR ASSIGNMENTS, v. 9, n. 1, p. 1-5, APR 2015. (10/51866-0)

BISSON-FILHO, ALEXANDRE W.; DISCOLA, KAREN F.; CASTELLEN, PATRICIA; BLASIOS, VALDIR; MARTINS, ALEXANDRE; SFORCA, MAURICIO L.; GARCIA, WANIUS; ZERI, ANA CAROLINA M.; ERICKSON, HAROLD P.; DESSEN, ANDREA; et al. FtsZ filament capping by MciZ, a developmental regulator of bacterial division. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 112, n. 17, p. 9-pg., 2015-04-28. (10/51866-0)