期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：28
页码：E3689-E3698
DOI：10.1073/pnas.1504281112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe rod shape of walled bacteria is determined by the peptidoglycan (PG) sacculus, but how rod shape is maintained as cells grow remains a fundamental question in bacterial cell biology. We have developed a coarse-grained modeling method to study rod shape maintenance. Individual PG remodeling enzymes, including transglycosylases, transpeptidases, and endopeptidases, are for the first time, to our knowledge, explicitly modeled to explore how they can coordinate to remodel a sacculus several orders of magnitude larger than the enzymes themselves. Rather than requiring top-down regulation of new PG insertion sites, our work shows that local coordination of the PG remodeling enzymes within discrete complexes can be sufficient to maintain the integrity and rod shape of the sacculus. Bacteria are surrounded by a peptidoglycan (PG) cell wall that must be remodeled to allow cell growth. While many structural details and properties of PG and the individual enzymes involved are known, how the process is coordinated to maintain cell integrity and rod shape is not understood. We have developed a coarse-grained method to simulate how individual transglycosylases, transpeptidases, and endopeptidases could introduce new material into an existing unilayer PG network. We find that a simple model with no enzyme coordination fails to maintain cell wall integrity and rod shape. We then iteratively analyze failure modes and explore different mechanistic hypotheses about how each problem might be overcome by the macromolecules involved. In contrast to a current theory, which posits that long MreB filaments are needed to coordinate PG insertion sites, we find that local coordination of enzyme activities in individual complexes can be sufficient to maintain cell integrity and rod shape. We also present possible molecular explanations for the existence of monofunctional transpeptidases and glycosidases (glycoside hydrolases), trimeric peptide crosslinks, cell twisting during growth, and synthesis of new strands in pairs.
