Mechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase
Abstract
Typhoid toxin is a virulence factor for the bacterial pathogen Salmonella Typhi, which causes typhoid fever in humans. After its synthesis by intracellular bacteria, typhoid toxin is secreted into the lumen of the Salmonella-containing vacuole by a secretion mechanism strictly dependent on TtsA, a specific muramidase that facilitates toxin transport through the peptidoglycan layer. Here we show that substrate recognition by TtsA depends on a discrete domain within its carboxy terminus, which targets the enzyme to the bacterial poles to recognize YcbB-edited peptidoglycan. Comparison of the atomic structures of TtsA bound to its substrate and that of a close homolog with different specificity identified specific determinants involved in substrate recognition. Combined with structure-guided mutagenesis and in vitro and in vivo crosslinking experiments, this study provides an unprecedented view of the mechanisms by which a muramidase recognizes its peptidoglycan substrate to facilitate protein secretion.
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Inst. of Allergy and Infectious Diseases; National Inst. of General Medical Sciences (NIGMS)
- OSTI Identifier:
- 1600820
- Grant/Contract Number:
- AC02-06CH11357; SC0012704; P41GM111244; KP1605010; AI079022
- Resource Type:
- Accepted Manuscript
- Journal Name:
- eLife
- Additional Journal Information:
- Journal Volume: 9; Journal Issue: 01, 2020; Journal ID: ISSN 2050-084X
- Publisher:
- eLife Sciences Publications, Ltd.
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Geiger, Tobias, Lara-Tejero, Maria, Xiong, Yong, and Galán, Jorge E. Mechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase. United States: N. p., 2020.
Web. doi:10.7554/eLife.53473.
Geiger, Tobias, Lara-Tejero, Maria, Xiong, Yong, & Galán, Jorge E. Mechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase. United States. https://doi.org/10.7554/eLife.53473
Geiger, Tobias, Lara-Tejero, Maria, Xiong, Yong, and Galán, Jorge E. Mon .
"Mechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase". United States. https://doi.org/10.7554/eLife.53473. https://www.osti.gov/servlets/purl/1600820.
@article{osti_1600820,
title = {Mechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase},
author = {Geiger, Tobias and Lara-Tejero, Maria and Xiong, Yong and Galán, Jorge E.},
abstractNote = {Typhoid toxin is a virulence factor for the bacterial pathogen Salmonella Typhi, which causes typhoid fever in humans. After its synthesis by intracellular bacteria, typhoid toxin is secreted into the lumen of the Salmonella-containing vacuole by a secretion mechanism strictly dependent on TtsA, a specific muramidase that facilitates toxin transport through the peptidoglycan layer. Here we show that substrate recognition by TtsA depends on a discrete domain within its carboxy terminus, which targets the enzyme to the bacterial poles to recognize YcbB-edited peptidoglycan. Comparison of the atomic structures of TtsA bound to its substrate and that of a close homolog with different specificity identified specific determinants involved in substrate recognition. Combined with structure-guided mutagenesis and in vitro and in vivo crosslinking experiments, this study provides an unprecedented view of the mechanisms by which a muramidase recognizes its peptidoglycan substrate to facilitate protein secretion.},
doi = {10.7554/eLife.53473},
journal = {eLife},
number = 01, 2020,
volume = 9,
place = {United States},
year = {Mon Jan 20 00:00:00 EST 2020},
month = {Mon Jan 20 00:00:00 EST 2020}
}
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