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Functional and structural characterization of the Bacillus's ZapA protein

Grant number: 12/15123-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2012
Effective date (End): August 31, 2016
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal Investigator:Ana Carolina de Mattos Zeri
Grantee:Maria Luiza Caldas Nogueira
Home Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia, Inovações e Comunicações (Brasil). Campinas , SP, Brazil
Associated scholarship(s):12/24916-1 - Structural studies of the Bacillus stearothermophilus's ZapA protein, BE.EP.DR

Abstract

Bacterial cell division occurs through the formation of a contracting macromolecular complex, that yields two daughter cells. The key event is the assembly of a protein complex that changes the bacterial envelope growth direction, formed by a ring of FtsZ proteins, known as the Z ring, in the central region of the cell. Once the Z ring is formed, other proteins are recruited to the site, giving rise to the functional divisome complex. The dynamics of the Z ring formation depends on the polymerization of FtsZ and other proteins that modulate its polymerization and the association between protofilaments. Although widely studied, little is known about the molecular mechanisms of interaction between the proteins involved in the divisome complex. There are two major groups of macromolecules in the complex, a few transmembrane proteins, which are the portion of the divisome responsible for synthesis of the bacterial cell wall, and a group of proteins in the cytoplasm, which modulate the Z ring dynamics through their spatio-temporal regulation. The proteins involved in the Z ring dynamics are split into positive and negative modulators. In B. subtilis, the main negative modulators systems are NOC and MinCD, the first of which prevents the Z ring formation on the nucleoid while the second inhibits the formation of the Z ring on the cell poles. The superposition of the two systems causes the ring to be formed in the central region of the cell, yielding two identical daughter cells. The positive modulators are those that aid the FtsZ polymerization and stabilize the interaction between protofilaments, formed by polymers of this protein, it is speculated that one of the modulators can also act to inhibit the hydrolysis of GTP to avoid the protofilaments's depolymerization. In this project we will focus on a positive modulator of FtsZ, the ZapA protein (Z ring Associated Protein A), which promotes the association of lateral filaments of FtsZ, leading to the formation of a ring from continuous filaments. Our goal is to characterize, at the molecular level, the interaction between FtsZ and ZapA, unraveling the structure of ZapA in B. stearothermophilus and seeking possible synthetic ligands that disrupt the function of ZapA, employing Nuclear Magnetic Resonance (NMR) structural techniques and Fragment Screening by NMR. A better understanding of the interaction between these two proteins may help in the understanding of the complex dynamics of bacterial cell division, and the search for new ligands may be useful in the search for new drugs with antibacterial action. (AU)

Scientific publications
(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)
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. Web of Science Citations: 1.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
NOGUEIRA, Maria Luiza Caldas. Functional and structural characterization of ZapA protein, involved in bacterial cell division. 2016. Doctoral Thesis - Universidade Estadual de Campinas, Instituto de Biologia.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.