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In\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            , the polyglycerolphosphate LTA molecule is synthesized by LtaS, a membrane-embedded enzyme with five N-terminal transmembrane helices (5TM domain) that are connected via a linker region to the C-terminal extracellular enzymatic domain (eLtaS). The LtaS enzyme is processed during bacterial growth, and the eLtaS domain is released from the bacterial membrane. Here we provide experimental evidence that the proteolytic cleavage following residues\n            <jats:sup>215<\/jats:sup>\n            Ala-Leu-Ala\n            <jats:sup>217<\/jats:sup>\n            is performed by the essential\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            signal peptidase SpsB, as depletion of\n            <jats:italic>spsB<\/jats:italic>\n            results in reduced LtaS processing. In addition, the introduction of a proline residue at the +1 position with respect to the cleavage site, a substitution known to inhibit signal peptidase-dependent cleavage, abolished LtaS processing at this site. It was further shown that the 5TM domain is crucial for enzyme function. The observation that the construction of hybrid proteins between two functional LtaS-type enzymes resulted in the production of proteins unable to synthesize LTA suggests that specific interactions between the 5TM and eLtaS domains are required for function. No enzyme activity was detected upon expression of the 5TM and eLtaS domains as separate fragments, indicating that the two domains cannot assemble postsynthesis to form a functional enzyme. Taken together, our data suggest that only the full-length LtaS enzyme is active in the LTA synthesis pathway and that the proteolytic cleavage step is used as a mechanism to irreversibly inactivate the enzyme.\n          <\/jats:p>","DOI":"10.1128\/jb.00369-11","type":"journal-article","created":{"date-parts":[[2011,7,23]],"date-time":"2011-07-23T04:47:30Z","timestamp":1311396450000},"page":"5279-5291","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":104,"title":["Proteolytic Cleavage Inactivates the Staphylococcus aureus Lipoteichoic Acid Synthase"],"prefix":"10.1128","volume":"193","author":[{"given":"Mirka E.","family":"W\u00f6rmann","sequence":"first","affiliation":[{"name":"Section of Microbiology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom"}]},{"given":"Nathalie T.","family":"Reichmann","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom"}]},{"given":"Cheryl L.","family":"Malone","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242"}]},{"given":"Alexander R.","family":"Horswill","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242"}]},{"given":"Angelika","family":"Gr\u00fcndling","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.182801"},{"key":"e_1_3_3_3_2","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1002\/pmic.200401218","article-title":"The extracellular and cytoplasmic proteomes of the non-virulent Bacillus anthracis strain UM23C1-2","volume":"5","author":"Antelmann H.","year":"2005","unstructured":"AntelmannH. . 2005. 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