Mechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase
- Yale Univ. School of Medicine, New Haven, CT (United States)
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.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- National Inst. of Allergy and Infectious Diseases; National Inst. of General Medical Sciences (NIGMS); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
- Grant/Contract Number:
- AC02-06CH11357; SC0012704
- OSTI ID:
- 1600820
- Alternate ID(s):
- OSTI ID: 1760481
- Journal Information:
- eLife, Journal Name: eLife Journal Issue: 01, 2020 Vol. 9; ISSN 2050-084X
- Publisher:
- eLife Sciences Publications, Ltd.Copyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
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