Finding new bacterial cell division regulators
Special Seminar – hosted by the ithree institute Professor Rick Lewis Newcastle University, United Kingdom
Professor Rick Lewis is the head of the Newcastle (UK) Structural Biology Laboratory, which comprises 7 PIs and a ~30 early career researchers. Prior to taking up his position in Newcastle in 2003, he held a Wellcome Trust Research Career Development Fellowship in Oxford University and post-docs in York University. His doctoral studies and Bachelor's degree are both in biochemistry. His lab currently focuses on the essential coordination of activities on either side of the cell membrane during bacterial cell division in Gram positive model organisms and pathogens, using structural biology and biochemistry approaches.
Bacterial cell division requires precise spatiotemporal regulation of the synthesis and the remodelling of the peptidoglycan layer that surrounds the cytoplasmic membrane. The GpsB protein regulates cell wall synthesis by binding to the penicillin binding proteins (PBPs) that polymerize and crosslink the glycan strands in cell wall peptidoglycan. Whilst the catalytic domains of the PBPs are located on the outside face of the cell, some PBPs also contain short cytoplasmic domains whose roles are poorly understood. We present here crystal structures of cytoplasmic PBP domains bound to the N-terminal domain of GpsB, and determined the critical features for the interaction of GpsB from diverse bacteria with their different PBP partners. We have used this information to predict and subsequently confirm novel partners of GpsB, and demonstrate the role that GpsB plays in modulating some of their activities. Given the importance of GpsB:PBP interactions in pathogenic bacteria, the crystal structure presents a promising starting point for design of new antibiotics and provides an important step forward in understanding the regulation of cell wall synthesis in cell division in several different important bacterial species.