Structural & Biochemical Characterisation of the Streptococcus pneumoniae Early-Stage Division Complex, FtsEX-PcsB.

Lead Research Organisation: University of Warwick
Department Name: School of Life Sciences

Abstract

Bacterial cell division is seen as one of the most highly conserved processes that occurs in that kingdom. FtsA (bacterial actin) works to anchor the Z-ring of FtsZ (bacterial tubulin) to the inner side of the cytoplasmic membrane, before other downstream components of the Divisome assemble in a highly coordinated manner. Two of these proteins are the ATPase FtsE, and the polytopic membrane protein FtsX that assemble as part of the early-stage Divisome assembly, which are required for subsequent assembly of further downstream components. Further to this, the FtsEX complex has been implemented in a peptidoglycan (PG) breakdown during daughter cell separation. To facilitate this, FtsX associates with the probable PG hydrolase, PcsB. These interaction as well as the control mechanisms are not well understood, and may provide crucial insight into future chemotherapeutic strategies that will govern the development of next-generation antibiotics.
We propose to study this system in the Gram-positive organism, Streptococcus pneumoniae; an opportunistic pathogen responsible for around 6000 deaths per year, predominantly in the elderly and children under 5. Recently, the S. pneumoniae PcsB crystal structure has been solved, revealing a V-shaped conformation, the active site containing CHAPS domain residing close to the coiled-coil domain. Based on the homologous interaction between FtsX and EnvC in E. coli, PcsB will need to undergo a conformational change in order to become activated. This may be facilitated by the ATPase action of FtsE, though the molecular mechanisms are unclear; which is in part what we propose to study in this project.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
2264827 Studentship BB/M01116X/1 30/09/2019 29/09/2023 Nicholas Stephen Briggs