Mechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase

eLife

Tobias Geiger¹  Jorge E Galán¹  Maria Lara-Tejero¹  Yong Xiong² 

[1] Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, United States;Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, United States;

关键词: protein secretion;    muramidase;    peptidoglycan remodeling;    bacterial envelope;    L-D transpeptidase;   

DOI  :  10.7554/eLife.53473

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown