Complement activation by ligand-driven juxtaposition of discrete pattern recognition complexes
Significance A salient feature of the immune system is its ability to discriminate self from nonself. We define the molecular mechanism governing activation of an ancient and central component: the lectin pathway of complement. The basis is the association of two proteases in distinct complexes with...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2014-09, Vol.111 (37), p.13445-13450 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Degn, Søren E. Kjaer, Troels R. Kidmose, Rune T. Jensen, Lisbeth Hansen, Annette G. Tekin, Mustafa Jensenius, Jens C. Andersen, Gregers R. Thiel, Steffen |
| description | Significance A salient feature of the immune system is its ability to discriminate self from nonself. We define the molecular mechanism governing activation of an ancient and central component: the lectin pathway of complement. The basis is the association of two proteases in distinct complexes with at least five pattern recognition molecules. Clustering of these complexes on ligand surfaces allows cross-activation of the proteases, which subsequently activate downstream factors to initiate a proteolytic cascade. This is conceptually similar to signaling by cellular receptors and could be viewed as cellular signaling turned inside out. Different pattern recognition complexes “talk to each other” to coordinate immune activation, which may impart differential activation based on recognition of simple vs. complex ligand patterns. |
| doi_str_mv | 10.1073/pnas.1406849111 |
| format | Article |
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We define the molecular mechanism governing activation of an ancient and central component: the lectin pathway of complement. The basis is the association of two proteases in distinct complexes with at least five pattern recognition molecules. Clustering of these complexes on ligand surfaces allows cross-activation of the proteases, which subsequently activate downstream factors to initiate a proteolytic cascade. This is conceptually similar to signaling by cellular receptors and could be viewed as cellular signaling turned inside out. Different pattern recognition complexes “talk to each other” to coordinate immune activation, which may impart differential activation based on recognition of simple vs. complex ligand patterns.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1406849111</identifier><identifier>PMID: 25197071</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Antibodies ; Bacteria ; Binding sites ; Biological Sciences ; cell communication ; complement ; Complement Activation ; Dimers ; Enzymes ; Ficolins ; Humans ; Immune system ; Lectins ; Lectins - metabolism ; Ligands ; Mannans ; Mannans - metabolism ; Mannose-Binding Lectin - metabolism ; Mannose-Binding Protein-Associated Serine Proteases - metabolism ; Models, Molecular ; Molecules ; Multiprotein Complexes - metabolism ; Oligomers ; Proteases ; Protein Binding ; Protein Multimerization ; proteinases ; proteolysis ; receptors ; Receptors, Pattern Recognition - metabolism ; Trimers ; Zymogens</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2014-09, Vol.111 (37), p.13445-13450</ispartof><rights>copyright © 1993–2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Sep 16, 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c591t-9cd1c744210ee9ce3b2af33bc75364bbab501d6db622f8afeb228e5f39a152553</citedby><cites>FETCH-LOGICAL-c591t-9cd1c744210ee9ce3b2af33bc75364bbab501d6db622f8afeb228e5f39a152553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/111/37.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/43043489$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/43043489$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25197071$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Degn, Søren E.</creatorcontrib><creatorcontrib>Kjaer, Troels R.</creatorcontrib><creatorcontrib>Kidmose, Rune T.</creatorcontrib><creatorcontrib>Jensen, Lisbeth</creatorcontrib><creatorcontrib>Hansen, Annette G.</creatorcontrib><creatorcontrib>Tekin, Mustafa</creatorcontrib><creatorcontrib>Jensenius, Jens C.</creatorcontrib><creatorcontrib>Andersen, Gregers R.</creatorcontrib><creatorcontrib>Thiel, Steffen</creatorcontrib><title>Complement activation by ligand-driven juxtaposition of discrete pattern recognition complexes</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Significance A salient feature of the immune system is its ability to discriminate self from nonself. We define the molecular mechanism governing activation of an ancient and central component: the lectin pathway of complement. The basis is the association of two proteases in distinct complexes with at least five pattern recognition molecules. Clustering of these complexes on ligand surfaces allows cross-activation of the proteases, which subsequently activate downstream factors to initiate a proteolytic cascade. This is conceptually similar to signaling by cellular receptors and could be viewed as cellular signaling turned inside out. Different pattern recognition complexes “talk to each other” to coordinate immune activation, which may impart differential activation based on recognition of simple vs. complex ligand patterns.</description><subject>Antibodies</subject><subject>Bacteria</subject><subject>Binding sites</subject><subject>Biological Sciences</subject><subject>cell communication</subject><subject>complement</subject><subject>Complement Activation</subject><subject>Dimers</subject><subject>Enzymes</subject><subject>Ficolins</subject><subject>Humans</subject><subject>Immune system</subject><subject>Lectins</subject><subject>Lectins - metabolism</subject><subject>Ligands</subject><subject>Mannans</subject><subject>Mannans - metabolism</subject><subject>Mannose-Binding Lectin - metabolism</subject><subject>Mannose-Binding Protein-Associated Serine Proteases - metabolism</subject><subject>Models, Molecular</subject><subject>Molecules</subject><subject>Multiprotein Complexes - metabolism</subject><subject>Oligomers</subject><subject>Proteases</subject><subject>Protein Binding</subject><subject>Protein Multimerization</subject><subject>proteinases</subject><subject>proteolysis</subject><subject>receptors</subject><subject>Receptors, Pattern Recognition - metabolism</subject><subject>Trimers</subject><subject>Zymogens</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v1DAQxS0EokvhzAmIxIVL2hl_Jb5UQitakCpxgF6xHMdZssrGwXZW7X9PslmWjwsnH95v3vjNI-QlwgVCwS6H3sQL5CBLrhDxEVkhKMwlV_CYrABokZec8jPyLMYtAChRwlNyRgWqAgpckW9rvxs6t3N9yoxN7d6k1vdZ9ZB17cb0dV6Hdu_6bDveJzP42B5k32R1G21wyWWDScmFPgvO-k2_6PZgeu_ic_KkMV10L47vObm7_vB1_TG__Xzzaf3-NrdCYcqVrdEWnFME55R1rKKmYayyhWCSV5WpBGAt60pS2pSmcRWlpRMNUwYFFYKdk6vFdxirnavtFCeYTg-h3ZnwoL1p9d9K337XG7_XHKVSgk8G744Gwf8YXUx6NwV0XWd658eosQR2uF7xf1RIBhIlhQl9-w-69WPop0vMFEeuKJt3Xy6UDT7G4JrTvxH0XLOea9a_a54mXv8Z98T_6nUCsiMwT57sEDUrNDLO55O9WpBtTD6cGM6AM16qSX-z6I3x2mxCG_XdFwooAZAzwYD9BPeXwvM</recordid><startdate>20140916</startdate><enddate>20140916</enddate><creator>Degn, Søren E.</creator><creator>Kjaer, Troels R.</creator><creator>Kidmose, Rune T.</creator><creator>Jensen, Lisbeth</creator><creator>Hansen, Annette G.</creator><creator>Tekin, Mustafa</creator><creator>Jensenius, Jens C.</creator><creator>Andersen, Gregers R.</creator><creator>Thiel, Steffen</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20140916</creationdate><title>Complement activation by ligand-driven juxtaposition of discrete pattern recognition complexes</title><author>Degn, Søren E. ; 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We define the molecular mechanism governing activation of an ancient and central component: the lectin pathway of complement. The basis is the association of two proteases in distinct complexes with at least five pattern recognition molecules. Clustering of these complexes on ligand surfaces allows cross-activation of the proteases, which subsequently activate downstream factors to initiate a proteolytic cascade. This is conceptually similar to signaling by cellular receptors and could be viewed as cellular signaling turned inside out. Different pattern recognition complexes “talk to each other” to coordinate immune activation, which may impart differential activation based on recognition of simple vs. complex ligand patterns.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>25197071</pmid><doi>10.1073/pnas.1406849111</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2014-09, Vol.111 (37), p.13445-13450 |
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| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Antibodies Bacteria Binding sites Biological Sciences cell communication complement Complement Activation Dimers Enzymes Ficolins Humans Immune system Lectins Lectins - metabolism Ligands Mannans Mannans - metabolism Mannose-Binding Lectin - metabolism Mannose-Binding Protein-Associated Serine Proteases - metabolism Models, Molecular Molecules Multiprotein Complexes - metabolism Oligomers Proteases Protein Binding Protein Multimerization proteinases proteolysis receptors Receptors, Pattern Recognition - metabolism Trimers Zymogens |
| title | Complement activation by ligand-driven juxtaposition of discrete pattern recognition complexes |
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