What Is Motion? Recent Advances in the Study of Molecular Movement Patterns of the Peptidoglycan Synthesis Machines

Abstract

How proteins move through space and time is a fundamental question in biology. While great strides have been made towards a mechanistic understanding of protein movement, many questions remain. We discuss the biological implications of motion in the context of the peptidoglycan (PG) synthesis machines. We review systems in several bacteria, including Escherichia coli , Bacillus subtilis , and Streptococcus pneumoniae , and present a comprehensive view of our current knowledge regarding movement dynamics. Discrepancies are also addressed since “one size does not fit all”. For bacteria to divide, new PG is synthesized and incorporated into the growing cell wall by complex multi-protein nanomachines consisting of PG synthases (transglycosylases [TG] and/or transpeptidases [TP]) as well as a variety of regulators and cytoskeletal factors. Advances in imaging capabilities and labeling methods have revealed that these machines are not static but rather circumferentially transit the cell via directed motion perpendicular to the long axis of model rod-shaped bacteria such as E. coli and B. subtilis . The enzymatic activity of the TG:TPs drives motion in some species, while motion is mediated by FtsZ treadmilling in others. In addition, both directed and diffusive motion of the PG synthases has been observed using single particle tracking technology. Here, we examine the biological role of diffusion regarding transit. Lastly, findings regarding the monofunctional transglycosylases (RodA and FtsW) as well as the Class A PG synthases are discussed. This minireview serves to showcase recent advances, broach mechanistic unknowns, and stimulate future areas of study.

Roles of RodZ and class A PBP1b in the assembly and regulation of the peripheral peptidoglycan elongasome in ovoid‐shaped cells of Streptococcus pneumoniaeD39

“…Movement of the assembled Rod elongasome is driven by sidewall PG synthesis itself, rather than by ATPase‐dependent treadmilling of MreB (Rohs & Bernhardt, 2021 ), with the MreB filaments serving as curvature‐sensing rudders (Hussain et al, 2018 ). Finally, in contrast to the parallel PG synthesis by the Rod elongasome, synthesis of sidewall PG by Class A PBPs appears to be largely non‐ordered, possibly filling in or reinforcing gaps left by the Rod system (Cho et al, 2016 ; Dion et al, 2019 ; Lamanna & Maurelli, 2022 ; Rohs & Bernhardt, 2021 ).…”

Elongasome core proteins and class A PBP1a display zonal, processive movement at the midcell ofStreptococcus pneumoniae

“…The CozE protein was also implicated in pneumococcal elongation PG synthesis (83). However, CozE did not behave equivalently to MreCD in transformation assays of function (84), and the exact function of pneumococcal CozE remains unknown. A pneumococcal TseB homolog renamed as CopD was recently reported to bind to bPBP2b and aPBP1a.…”

Roles of RodZ and Class A PBP1b in the Assembly and Regulation of the Peripheral Peptidoglycan Elongasome in Ovoid-Shaped Cells ofStreptococcus pneumoniaeD39

“…Movement of the assembled Rod elongasome is driven by sidewall PG synthesis itself, rather than by ATPase-dependent treadmilling of MreB (Rohs & Bernhardt, 2021), with the MreB filaments serving as curvature-sensing rudders (Hussain et al ., 2018). Finally, in contrast to the parallel PG synthesis by the Rod elongasome, synthesis of sidewall PG by Class A PBPs appears to be largely non-ordered, possibly filling in or reinforcing gaps left by the Rod system (Cho et al ., 2016, Dion et al ., 2019, Lamanna & Maurelli, 2022, Rohs & Bernhardt, 2021).…”