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Tanapoxvirus (TANV) is a large double\u2010stranded DNA virus belonging to the\n                      <jats:italic>poxviridae<\/jats:italic>\n                      that causes mild monkeypox\u2010like infections in humans and primates. TANV encodes for a putative apoptosis inhibitory protein 16L. We show that TANV16L is able to bind to a range of peptides spanning the BH3 motif of human proapoptotic Bcl\u20102 proteins and is able to counter growth arrest of yeast induced by human Bak and Bax. We then determined the crystal structures of TANV16L bound to three identified interactors, Bax, Bim and Puma BH3. TANV16L adopts a globular Bcl\u20102 fold comprising 7 \u03b1\u2010helices and utilizes the canonical Bcl\u20102 binding groove to engage proapoptotic host cell Bcl\u20102 proteins. Unexpectedly, TANV16L is able to adopt both a monomeric and a domain\u2010swapped dimeric topology where the \u03b11 helix from one protomer is swapped into a neighbouring unit. Despite adopting two different oligomeric forms, the canonical ligand binding groove in TANV16L remains unchanged from monomer to domain\u2010swapped dimer. Our results provide a structural and mechanistic basis for tanapoxvirus\u2010mediated inhibition of host cell apoptosis and reveal the capacity of Bcl\u20102 proteins to adopt differential oligomeric states whilst maintaining the canonical ligand binding groove in an unchanged state.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Database<\/jats:title>\n                    <jats:p>\n                      Structural data are available in the Protein Data Bank (PDB) under the accession numbers\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/6TPQ\">6TPQ<\/jats:ext-link>\n                      ,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/6TQQ\">6TQQ<\/jats:ext-link>\n                      and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/6TRR\">6TRR<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/febs.15365","type":"journal-article","created":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T00:41:27Z","timestamp":1589589687000},"page":"3733-3750","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Structural insight into tanapoxvirus\u2010mediated inhibition of apoptosis"],"prefix":"10.1111","volume":"287","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9185-6063","authenticated-orcid":false,"given":"Chathura D.","family":"Suraweera","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Genetics La Trobe Institute for Molecular Science La Trobe University Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Ishtiaq","family":"Anasir","sequence":"additional","affiliation":[{"name":"Department of 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