{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:22:45Z","timestamp":1793089365367,"version":"4.5.0"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR-10-LABX-62-IBEID, ANR 20-PAMR-0011-TheraEPI"],"award-info":[{"award-number":["ANR-10-LABX-62-IBEID, ANR 20-PAMR-0011-TheraEPI"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR-18-CE15-0005-01"],"award-info":[{"award-number":["ANR-18-CE15-0005-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002915","name":"Fondation de la Recherche M\u00e9dicale","doi-asserted-by":"crossref","award":["EQU201903007847"],"award-info":[{"award-number":["EQU201903007847"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002879","name":"Canadian HIV Trials Network, Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["MOP-48370"],"award-info":[{"award-number":["MOP-48370"]}],"id":[{"id":"10.13039\/501100002879","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2023,10,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Legionella pneumophila<\/jats:italic>\n            is a bacterial pathogen ubiquitous in natural and man-made aquatic environments, where it replicates in protozoa. Its intracellular life cycle depends on the establishment of a\n            <jats:italic>Legionella<\/jats:italic>\n            -containing vacuole (LCV) where the bacteria replicate. To form the LCV,\n            <jats:italic>L. pneumophila<\/jats:italic>\n            depends on a type-4 secretion system that secretes more than 300 proteins in the host cell. Among these is RomA that encodes an N-terminal catalytic methyltransferase domain with a SET fold and a C-terminal domain containing six ankyrin repeats. We have reported that the SET domain has histone methyltransferase activity and specifically methylates lysine 14 of histone H3 during infection; however, the role of the ankyrin repeats is unknown. Here, we report the structure of RomA co-crystallized with a 15-mer peptide corresponding to the N-terminal tail of histone H3 at 2.2 \u00c5. This structure revealed that the N-terminal arm of the peptide from Thr3-Ala7 binds to the ankyrin repeat domain and the C-terminal arm from Gly13-Arg17 and interacts with the SET domain, inserting Lys14 into the active site for methylation. Importantly, the interactions of the five N-terminal residues of the H3-peptide with the ankyrin domains account for ~50% of the peptide-RomA contacts, predicting that the ankyrin domains of RomA are essential for histone H3 binding and subsequent lysine methylation.\n            <jats:italic>In vitro<\/jats:italic>\n            enzymatic activity and binding assays confirmed these predictions. Thus, the six ankyrin domains are essential for chromatin binding, thereby allowing the SET domain to fulfill its histone transferase activity and to modify the host chromatin to the advantage of the pathogen.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>Legionella pneumophila<\/jats:italic>\n              is an intracellular bacterium responsible of Legionnaires\u2019 disease, a severe pneumonia that is often fatal when not treated promptly. The pathogen\u2019s ability to efficiently colonize the host resides in its ability to replicate intracellularly. Essential for intracellular replication is translocation of many different protein effectors\n              <jats:italic>via<\/jats:italic>\n              a specialized secretion system. One of them, called RomA, binds and directly modifies the host chromatin at a unique site (tri-methylation of lysine 14 of histone H3 [H3K14me]). However, the molecular mechanisms of binding are not known. Here, we resolve this question through structural characterization of RomA together with the H3 peptide. We specifically reveal an active role of the ankyrin repeats located in its C-terminal in the interaction with the histone H3 tail. Indeed, without the ankyrin domains, RomA loses its ability to act as histone methyltransferase. These results discover the molecular mechanisms by which a bacterial histone methyltransferase that is conserved in\n              <jats:italic>L. pneumophila<\/jats:italic>\n              strains acts to modify chromatin.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.01655-23","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T13:02:08Z","timestamp":1696510928000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["The SET and ankyrin domains of the secreted\n            <i>Legionella pneumophila<\/i>\n            histone methyltransferase work together to modify host chromatin"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3710-0115","authenticated-orcid":false,"given":"Monica","family":"Rolando","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, Biologie des Bact\u00e9ries Intracellulaires , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivy Yeuk","family":"Wah Chung","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan , Saskatoon, Saskatchewan, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caishuang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan , Saskatoon, Saskatchewan, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Gomez-Valero","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, Biologie des Bact\u00e9ries Intracellulaires , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"England","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, Plateforme de 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