{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:13:13Z","timestamp":1790691193346,"version":"4.1.0"},"reference-count":47,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI079022"],"award-info":[{"award-number":["AI079022"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.7554\/elife.53473","type":"journal-article","created":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T08:00:25Z","timestamp":1579507225000},"source":"Crossref","is-referenced-by-count":26,"title":["Mechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8528-2849","authenticated-orcid":true,"given":"Tobias","family":"Geiger","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1339-0859","authenticated-orcid":true,"given":"Maria","family":"Lara-Tejero","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6531-0355","authenticated-orcid":true,"given":"Jorge E","family":"Gal\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2020,1,20]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: a comprehensive Python-based system for macromolecular structure solution","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Crystallographica Section D Biological Crystallography"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1046\/j.1365-2958.1999.01527.x","article-title":"pH-dependent secretion of SseB, a product of the SPI-2 type III secretion system of Salmonella typhimurium","volume":"33","author":"Beuz\u00f3n","year":"1999","journal-title":"Molecular Microbiology"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01219-14","article-title":"Peptidoglycan synthesis machinery in Agrobacterium tumefaciens during unipolar growth and cell division","volume":"5","author":"Cameron","year":"2014","journal-title":"mBio"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/j.chom.2016.10.005","article-title":"Receptor-Mediated sorting of typhoid toxin during its export from Salmonella Typhi-Infected cells","volume":"20","author":"Chang","year":"2016","journal-title":"Cell Host & Microbe"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007704","article-title":"Unique features in the intracellular transport of typhoid toxin revealed by a genome-wide screen","volume":"15","author":"Chang","year":"2019","journal-title":"PLOS Pathogens"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s10930-019-09862-3","article-title":"The rich tapestry of bacterial protein translocation systems","volume":"38","author":"Christie","year":"2019","journal-title":"The Protein Journal"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1107\/S0907444994003112","article-title":"The CCP4 suite: programs for protein crystallography","volume":"50","author":"Collaborative Computational Project, Number 4","year":"1994","journal-title":"Acta Crystallographica Section D Biological Crystallography"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/nrmicro3456","article-title":"Secretion systems in Gram-negative Bacteria: structural and mechanistic insights","volume":"13","author":"Costa","year":"2015","journal-title":"Nature Reviews Microbiology"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1107\/S0907444906022116","article-title":"The buccaneer software for automated model building. 1. 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