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Staphylococcal superantigen-like (SSL) proteins, expressed by all known\n                    <jats:italic>S. aureus<\/jats:italic>\n                    strains, are shown to be involved in immune evasion during\n                    <jats:italic>S. aureus<\/jats:italic>\n                    infection. Here, we show that SSL10, an SSL family protein, exhibits potent cytotoxicity against human cells (HEK293T and HUVEC) by inducing necroptosis upon binding to its receptor TNFR1 on the cell membrane. After binding, two distinct signaling pathways are activated downstream of TNFR1 in a RIPK3-dependent manner, i.e., the RIPK1-RIPK3-MLKL and RIPK3-CaMKII-mitochondrial permeability transition pore (mPTP) pathways. Knockout of\n                    <jats:italic>ssl10<\/jats:italic>\n                    in\n                    <jats:italic>S. aureus<\/jats:italic>\n                    significantly reduces cytotoxicity of the culture supernatants of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    , indicating that SSL10 is involved in extracellular cytotoxicity during infection. We determined the crystal structure of SSL10 at 1.9\u2009\u00c5 resolution and identified a positively charged surface of SSL10 responsible for TNFR1 binding and cytotoxic activity. This study thus provides the description of cytotoxicity through induction of necroptosis by the SSL10 protein, and a potential target for clinical treatment of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    -associated diseases.\n                  <\/jats:p>","DOI":"10.1038\/s42003-022-03752-8","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T14:03:09Z","timestamp":1660312989000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Staphylococcal superantigen-like protein 10 induces necroptosis through TNFR1 activation of RIPK3-dependent signal pathways"],"prefix":"10.1038","volume":"5","author":[{"given":"Nan","family":"Jia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanbiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengliang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1196-3190","authenticated-orcid":false,"given":"Yue","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2648-9783","authenticated-orcid":false,"given":"Jianye","family":"Zang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7035-6182","authenticated-orcid":false,"given":"Xi","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0660-1168","authenticated-orcid":false,"given":"Jinfeng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,12]]},"reference":[{"key":"3752_CR1","doi-asserted-by":"publisher","first-page":"S106","DOI":"10.1111\/j.1444-0903.2005.00984.x","volume":"35","author":"RJ Murray","year":"2005","unstructured":"Murray, R. 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