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dc.contributor.authorSwaminathan, Chittoor P.
dc.contributor.authorBrown, Patrick H.
dc.contributor.authorRoychowdhury, Abhijit
dc.contributor.authorWang, Qian
dc.contributor.authorGuan, Rongjin
dc.contributor.authorSilverman, Neal S.
dc.contributor.authorGoldman, William E.
dc.contributor.authorBoons, Geert-Jan
dc.contributor.authorMariuzza, Roy A.
dc.date2022-08-11T08:09:08.000
dc.date.accessioned2022-08-23T16:18:58Z
dc.date.available2022-08-23T16:18:58Z
dc.date.issued2006-01-13
dc.date.submitted2008-12-19
dc.identifier.citationProc Natl Acad Sci U S A. 2006 Jan 17;103(3):684-9. Epub 2006 Jan 9. <a href="http://dx.doi.org/10.1073/pnas.0507656103">Link to article on publisher's site</a>
dc.identifier.issn0027-8424 (Print)
dc.identifier.doi10.1073/pnas.0507656103
dc.identifier.pmid16407132
dc.identifier.urihttp://hdl.handle.net/20.500.14038/34936
dc.description.abstractThe innate immune system constitutes the first line of defense against microorganisms in both vertebrates and invertebrates. Although much progress has been made toward identifying key receptors and understanding their role in host defense, far less is known about how these receptors recognize microbial ligands. Such studies have been severely hampered by the need to purify ligands from microbial sources and a reliance on biological assays, rather than direct binding, to monitor recognition. We used synthetic peptidoglycan (PGN) derivatives, combined with microcalorimetry, to define the binding specificities of human and insect peptidoglycan recognition proteins (PGRPs). We demonstrate that these innate immune receptors use dual strategies to distinguish between PGNs from different bacteria: one based on the composition of the PGN peptide stem and another that senses the peptide bridge crosslinking the stems. To pinpoint the site of PGRPs that mediates discrimination, we engineered structure-based variants having altered PGN-binding properties. The plasticity of the PGRP-binding site revealed by these mutants suggests an intrinsic capacity of the innate immune system to rapidly evolve specificities to meet new microbial challenges.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=16407132&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1073/pnas.0507656103
dc.subjectAnimals
dc.subjectCarrier Proteins
dc.subjectDrosophila
dc.subjectHumans
dc.subjectLigands
dc.subjectPeptidoglycan
dc.subjectProtein Binding
dc.subjectSequence Alignment
dc.subjectVirulence Factors, Bordetella
dc.subjectImmunology and Infectious Disease
dc.titleDual strategies for peptidoglycan discrimination by peptidoglycan recognition proteins (PGRPs)
dc.typeJournal Article
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.volume103
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/infdis_pp/16
dc.identifier.contextkey684327
html.description.abstract<p>The innate immune system constitutes the first line of defense against microorganisms in both vertebrates and invertebrates. Although much progress has been made toward identifying key receptors and understanding their role in host defense, far less is known about how these receptors recognize microbial ligands. Such studies have been severely hampered by the need to purify ligands from microbial sources and a reliance on biological assays, rather than direct binding, to monitor recognition. We used synthetic peptidoglycan (PGN) derivatives, combined with microcalorimetry, to define the binding specificities of human and insect peptidoglycan recognition proteins (PGRPs). We demonstrate that these innate immune receptors use dual strategies to distinguish between PGNs from different bacteria: one based on the composition of the PGN peptide stem and another that senses the peptide bridge crosslinking the stems. To pinpoint the site of PGRPs that mediates discrimination, we engineered structure-based variants having altered PGN-binding properties. The plasticity of the PGRP-binding site revealed by these mutants suggests an intrinsic capacity of the innate immune system to rapidly evolve specificities to meet new microbial challenges.</p>
dc.identifier.submissionpathinfdis_pp/16
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pages684-9


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