{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:13:11Z","timestamp":1790737991706,"version":"4.1.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["75N93022C00035, HHSN272201700060C"],"award-info":[{"award-number":["75N93022C00035, HHSN272201700060C"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Canadian Government | Natural Sciences and Engineering Research Council of Canada","award":["Discovery grant"],"award-info":[{"award-number":["Discovery grant"]}]},{"name":"Alberta Graduate Excellence Scholarship"},{"name":"Canadian Government | Canadian Institutes of Health Research","award":["Project grant"],"award-info":[{"award-number":["Project grant"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,3,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The survival of\n              <jats:italic>Legionella<\/jats:italic>\n              spp. as intracellular pathogens relies on the combined action of protein effectors delivered inside their eukaryotic hosts by the Dot\/Icm (\n              <jats:underline>d<\/jats:underline>\n              efective in\n              <jats:underline>o<\/jats:underline>\n              rganelle\n              <jats:underline>t<\/jats:underline>\n              rafficking\/\n              <jats:underline>i<\/jats:underline>\n              ntra\n              <jats:underline>c<\/jats:underline>\n              ellular\n              <jats:underline>m<\/jats:underline>\n              ultiplication) type IVb secretion system. The specific repertoire of effector arsenals varies dramatically across over 60 known species of this genera with\n              <jats:italic>Legionella pneumophila<\/jats:italic>\n              responsible for most cases of Legionnaires\u2019 disease in humans encoding over 360 Dot\/Icm effectors. However, a small subset of \u201ccore\u201d effectors appears to be conserved across all\n              <jats:italic>Legionella<\/jats:italic>\n              species raising an intriguing question of their role in these bacteria\u2019s pathogenic strategy, which for most of these effectors remains unknown.\n              <jats:italic>L. pneumophila<\/jats:italic>\n              Lpg0103 effector, also known as VipF, represents one of the core effector families that features a tandem of Gcn5-related N-acetyltransferase (GNAT) domains. Here, we present the crystal structure of the Lha0223, the VipF representative from\n              <jats:italic>Legionella hackeliae<\/jats:italic>\n              in complex with acetyl-coenzyme A determined to 1.75 \u00c5 resolution. Our structural analysis suggested that this effector family shares a common fold with the two GNAT domains forming a deep groove occupied by residues conserved across VipF homologs. Further analysis suggested that only the C-terminal GNAT domain of VipF effectors retains the active site composition compatible with catalysis, whereas the N-terminal GNAT domain binds the ligand in a non-catalytical mode. We confirmed this by\n              <jats:italic>in vitro<\/jats:italic>\n              enzymatic assays which revealed VipF activity not only against generic small molecule substrates, such as chloramphenicol, but also against poly-L-lysine and histone-derived peptides. We identified the human eukaryotic translation initiation factor 3 (eIF3) complex co-precipitating with Lpg0103 and demonstrated the direct interaction between the several representatives of the VipF family, including Lpg0103 and Lha0223 with the K subunit of eIF3. According to our data, these interactions involve primarily the C-terminal tail of eIF3-K containing two lysine residues that are acetylated by VipF. VipF catalytic activity results in the suppression of eukaryotic protein translation\n              <jats:italic>in vitro<\/jats:italic>\n              , revealing the potential function of VipF \u201ccore\u201d effectors in\n              <jats:italic>Legionella<\/jats:italic>\n              \u2019s pathogenic strategy.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                By translocating effectors inside the eukaryotic host cell, bacteria can modulate host cellular processes in their favor.\n                <jats:italic>Legionella<\/jats:italic>\n                species, which includes the pneumonia-causing\n                <jats:italic>Legionella pneumophila,<\/jats:italic>\n                encode a widely diverse set of effectors with only a small subset that is conserved across this genus. Here, we demonstrate that one of these conserved effector families, represented by\n                <jats:italic>L. pneumophila<\/jats:italic>\n                VipF (Lpg0103), is a tandem Gcn5-related N-acetyltransferase interacting with the K subunit of human eukaryotic initiation factor 3 complex. VipF catalyzes the acetylation of lysine residues on the C-terminal tail of the K subunit, resulting in the suppression of eukaryotic translation initiation factor 3-mediated protein translation\n                <jats:italic>in vitro<\/jats:italic>\n                . These new data provide the first insight into the molecular function of this pathogenic factor family common across\n                <jats:italic>Legionellae<\/jats:italic>\n                .\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/mbio.03221-23","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T17:35:11Z","timestamp":1707500111000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["An acetyltransferase effector conserved across\n            <i>Legionella<\/i>\n            species targets the eukaryotic eIF3 complex to modulate protein translation"],"prefix":"10.1128","volume":"15","author":[{"given":"Lukas","family":"Syriste","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3997-0265","authenticated-orcid":false,"given":"Deepak T.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Stogios","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering and Applied Chemistry, Toronto University, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Skarina","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering and Applied Chemistry, Toronto University, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhruvin","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Microbiology, 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