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dc.contributor.authorLatz, Eicke
dc.contributor.authorVerma, Anjali
dc.contributor.authorVisintin, Alberto
dc.contributor.authorGong, Mei
dc.contributor.authorSirois, Cherilyn M.
dc.contributor.authorKlein, Dionne C. G.
dc.contributor.authorMonks, Brian G.
dc.contributor.authorMcKnight, C. James
dc.contributor.authorLamphier, Marc S.
dc.contributor.authorDuprex, W. Paul
dc.contributor.authorEspevik, Terje
dc.contributor.authorGolenbock, Douglas T.
dc.date2022-08-11T08:08:58.000
dc.date.accessioned2022-08-23T16:14:04Z
dc.date.available2022-08-23T16:14:04Z
dc.date.issued2007-06-19
dc.date.submitted2008-09-22
dc.identifier.citationNat Immunol. 2007 Jul;8(7):772-9. Epub 2007 Jun 17. <a href="http://dx.doi.org/10.1038/ni1479">Link to article on publisher's site</a>
dc.identifier.issn1529-2908 (Print)
dc.identifier.doi10.1038/ni1479
dc.identifier.pmid17572678
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33774
dc.description.abstractMicrobial and synthetic DNA rich in CpG dinucleotides stimulates Toll-like receptor 9 (TLR9), whereas DNA lacking CpG either is inert or can inhibit TLR9 activation. The molecular mechanisms by which TLR9 becomes activated or is inhibited are not well understood. Here we show that TLR9 bound to stimulatory and inhibitory DNA; however, only stimulatory DNA led to substantial conformational changes in the TLR9 ectodomain. In the steady state, 'inactive' TLR9 homodimers formed in an inactivated conformation. Binding of DNA containing CpG, but not of DNA lacking CpG, to TLR9 dimers resulted in allosteric changes in the TLR9 cytoplasmic signaling domains. In endosomes, conformational changes induced by DNA containing CpG resulted in close apposition of the cytoplasmic signaling domains, a change that is probably required for the recruitment of signaling adaptor molecules. Our results indicate that the formation of TLR9 dimers is not sufficient for its activation but instead that TLR9 activation is regulated by conformational changes induced by DNA containing CpG.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17572678&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1038/ni1479
dc.subjectAllosteric Regulation; Cell Line; CpG Islands; Humans; Ligands; Oligodeoxyribonucleotides; Protein Binding; Protein Conformation; Toll-Like Receptor 9
dc.subjectImmunology and Infectious Disease
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleLigand-induced conformational changes allosterically activate Toll-like receptor 9
dc.typeJournal Article
dc.source.journaltitleNature immunology
dc.source.volume8
dc.source.issue7
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/435
dc.identifier.contextkey635310
html.description.abstract<p>Microbial and synthetic DNA rich in CpG dinucleotides stimulates Toll-like receptor 9 (TLR9), whereas DNA lacking CpG either is inert or can inhibit TLR9 activation. The molecular mechanisms by which TLR9 becomes activated or is inhibited are not well understood. Here we show that TLR9 bound to stimulatory and inhibitory DNA; however, only stimulatory DNA led to substantial conformational changes in the TLR9 ectodomain. In the steady state, 'inactive' TLR9 homodimers formed in an inactivated conformation. Binding of DNA containing CpG, but not of DNA lacking CpG, to TLR9 dimers resulted in allosteric changes in the TLR9 cytoplasmic signaling domains. In endosomes, conformational changes induced by DNA containing CpG resulted in close apposition of the cytoplasmic signaling domains, a change that is probably required for the recruitment of signaling adaptor molecules. Our results indicate that the formation of TLR9 dimers is not sufficient for its activation but instead that TLR9 activation is regulated by conformational changes induced by DNA containing CpG.</p>
dc.identifier.submissionpathgsbs_sp/435
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pages772-9
dc.contributor.studentCherilyn M. Sirois


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