| Grant number: | 12/15123-8 |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| Start date: | October 01, 2012 |
| End date: | August 31, 2016 |
| Field of knowledge: | Biological Sciences - Biochemistry - Chemistry of Macromolecules |
| Principal Investigator: | Ana Carolina de Mattos Zeri |
| Grantee: | Maria Luiza Caldas Nogueira |
| Host Institution: | Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (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) | |
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