{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:07:41Z","timestamp":1785424061775,"version":"3.56.0"},"posted":{"date-parts":[[2025,10,23]]},"group-title":"Microbiology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["P20GM113117"],"award-info":[{"award-number":["P20GM113117"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/05hs6h993","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/05p1j8758","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  <jats:italic>Legionella pneumophila<\/jats:italic>\n                  is an opportunistic human pathogen that causes atypical pneumonia called Legionnaires\u2019 Disease. To replicate within host cells,\n                  <jats:italic>L. pneumophila<\/jats:italic>\n                  injects up to 330 effector proteins into the host cytosol via a Dot\/Icm type IV secretion system. Several effectors, called metaeffectors, regulate the activity of other effectors within infected host cells through direct protein-protein interactions. LegA11 (AnkJ\/Lpg0436) has been identified as a putative metaeffector of SidL (Ceg14\/Lpg0437), one of eight\n                  <jats:italic>L. pneumophila<\/jats:italic>\n                  effectors that inhibit host mRNA translation. LegA11 binds and suppresses SidL enzymatic activity, but the molecular basis of this regulation and impact on mRNA translation are unknown. Here, we present the crystal structure of SidL in complex with LegA11 to a resolution of 2.4 \u00c5, revealing a high-affinity 1:1 complex with an extensive interaction interface of \u223c2300 \u00c5\u00b2. Using isothermal titration calorimetry, we determined a dissociation constant of 1.8 nM.\n                  <jats:italic>In vitro<\/jats:italic>\n                  translation assays demonstrate that SidL inhibits mRNA translation, and this activity is completely suppressed by LegA11. Mutagenesis of key interface residues in LegA11 disrupts complex formation and abolishes its metaeffector activity, confirming that LegA11 regulates SidL through direct protein-protein interaction. These findings establish LegA11 as a\n                  <jats:italic>bona fide<\/jats:italic>\n                  metaeffector that contributes to suppression of host mRNA translation by\n                  <jats:italic>L. pneumophila<\/jats:italic>\n                  .\n                <\/jats:p>","DOI":"10.1101\/2025.10.23.683979","type":"posted-content","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T03:05:17Z","timestamp":1761275117000},"source":"Crossref","is-referenced-by-count":2,"title":["Crystal structure of the\n                  <i>Legionella pneumophila<\/i>\n                  effector SidL (Lpg0437) in complex with its metaeffector LegA11 (Lpg0436)"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1597-7901","authenticated-orcid":false,"given":"Dominik A.","family":"Machtens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carissa A.","family":"Hutchison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9098-7563","authenticated-orcid":false,"given":"Ashley M.","family":"Stein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6101-9667","authenticated-orcid":false,"given":"Jan","family":"Eberhage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8281-5024","authenticated-orcid":false,"given":"Jonas M.","family":"Willerding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7422-618X","authenticated-orcid":false,"given":"Susanne","family":"Eschenburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2278-1405","authenticated-orcid":false,"given":"Stephanie R.","family":"Shames","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F.","family":"Reubold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025102708400956000_2025.10.23.683979v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2019.06.012"},{"key":"2025102708400956000_2025.10.23.683979v1.2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.001187"},{"key":"2025102708400956000_2025.10.23.683979v1.3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012419-032742"},{"key":"2025102708400956000_2025.10.23.683979v1.4","doi-asserted-by":"publisher","DOI":"10.1128\/jb.00324-24"},{"key":"2025102708400956000_2025.10.23.683979v1.5","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00076"},{"key":"2025102708400956000_2025.10.23.683979v1.6","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01798-07"},{"key":"2025102708400956000_2025.10.23.683979v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.01.006"},{"key":"2025102708400956000_2025.10.23.683979v1.8","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03221-23"},{"key":"2025102708400956000_2025.10.23.683979v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01248-z"},{"key":"2025102708400956000_2025.10.23.683979v1.10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001216"},{"key":"2025102708400956000_2025.10.23.683979v1.11","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10020108"},{"key":"2025102708400956000_2025.10.23.683979v1.12","doi-asserted-by":"crossref","unstructured":"Joseph AM , Pohl AE , Ball TJ , Abram TG , Johnson DK , Geisbrecht B V , et al. The Legionella pneumophila metaeffector Lpg2505 (MesI) regulates SidI-mediated translation inhibition and novel glycosyl hydrolase activity. Infect Immun. 2020. doi:IAI.00853-19 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