Publication: Mycobacterium tuberculosis FtsX extracellular domain activates the peptidoglycan hydrolase, RipC
No Thumbnail Available
Open/View Files
Date
2014
Published Version
Journal Title
Journal ISSN
Volume Title
Publisher
National Academy of Sciences
The Harvard community has made this article openly available. Please share how this access benefits you.
Citation
Mavrici, D., M. J. Marakalala, J. M. Holton, D. M. Prigozhin, C. L. Gee, Y. J. Zhang, E. J. Rubin, and T. Alber. 2014. “Mycobacterium Tuberculosis FtsX Extracellular Domain Activates the Peptidoglycan Hydrolase, RipC.” Proceedings of the National Academy of Sciences 111 (22): 8037–42. https://doi.org/10.1073/pnas.1321812111.
Research Data
Abstract
Bacterial growth and cell division are coordinated with hydrolysis of the peptidoglycan (PG) layer of the cell wall, but the mechanisms of regulation of extracellular PG hydrolases are not well understood. Here we report the biochemical, structural, and genetic analysis of the Mycobacterium tuberculosis homolog of the transmembrane PG-hydrolase regulator, FtsX. The purified FtsX extracellular domain binds the PG peptidase Rv2190c/RipC N-terminal segment, causing a conformational change that activates the enzyme. Deletion of ftsEX and ripC caused similar phenotypes in Mycobacterium smegmatis, as expected for genes in a single pathway. The crystal structure of the FtsX extracellular domain reveals an unprecedented fold containing two lobes connected by a flexible hinge. Mutations in the hydrophobic cleft between the lobes reduce RipC binding in vitro and inhibit FtsX function in M. smegmatis. These studies suggest how FtsX recognizes RipC and support a model inwhich a conformational change in FtsX links the cell division apparatus with PG hydrolysis.
Description
Other Available Sources
Keywords
Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material (LAA), as set forth at Terms of Service