Analogous Interactions in Initiating Complexes of the Classical and Lectin Pathways of Complement

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dc.contributor.authorPhillips, A. E.en
dc.contributor.authorToth, J.en
dc.contributor.authorDodds, A. W.en
dc.contributor.authorVenkatraman Girija, U.en
dc.contributor.authorFurze, Christopher M.en
dc.contributor.authorPala, E.en
dc.contributor.authorSim, R.B.en
dc.contributor.authorReid, K. B. M.en
dc.contributor.authorSchwaeble, W. J.en
dc.contributor.authorSchmid, R.en
dc.contributor.authorKeeble, A. H.en
dc.contributor.authorWallis, R.en
dc.date.accessioned2015-06-02T13:16:55Z
dc.date.available2015-06-02T13:16:55Z
dc.date.issued2009-06
dc.description.abstractThe classical and lectin pathways of complement activation neutralize pathogens and stimulate key immunological processes. Both pathways are initiated by collagen-containing, soluble pattern recognition molecules associated with specific serine proteases. In the classical pathway, C1q binds to Ab-Ag complexes or bacterial surfaces to activate C1r and C1s. In the lectin pathway, mannan-binding lectin and ficolins bind to carbohydrates on pathogens to activate mannan-binding lectin-associated serine protease 2. To characterize the interactions leading to classical pathway activation, we have analyzed binding between human C1q, C1r, and C1s, which associate to form C1, using full-length and truncated protease components. We show that C1r and C1s bind to C1q independently. The CUB1-epidermal growth factor fragments contribute most toward binding, but CUB2 of C1r, but not of C1s, is also important. Each C1rs tetramer presents a total of six binding sites, one for each of the collagenous domains of C1q. We also demonstrate that subcomponents of the lectin and classical pathways cross-interact. Thus, although the stoichiometries of complexes differ, interactions are analogous, with equivalent contacts between recognition and protease subcomponents. Importantly, these new data are contrary to existing models of C1 and enable us to propose a new model using mannan-binding lectin-mannan-binding lectin-associated serine protease interactions as a template.en
dc.fundernaen
dc.identifier.citationPhillips, A.E., Toth, J., Dodds, A.W., Venkatraman Girija, U., Furze, C.M., Pala, E., Sim, R.B., Reid, K.B.M., Schwaeble, W.J., Schmid, R., Keeble, A.H. and Wallis, R. (2009) Analogous Interactions in Initiating Complexes of the Classical and Lectin Pathways of Complement. The Journal of Immunololgy, 182 (12), pp. 7708-7717en
dc.identifier.doihttps://doi.org/10.4049/jimmunol.0900666
dc.identifier.urihttp://hdl.handle.net/2086/11001
dc.language.isoenen
dc.peerreviewedYesen
dc.projectidnaen
dc.publisherThe American Association of Immunologistsen
dc.researchgroupInfectious Disease Research Group
dc.researchinstituteInstitute for Allied Health Sciences Researchen
dc.subjectcomplement activationen
dc.titleAnalogous Interactions in Initiating Complexes of the Classical and Lectin Pathways of Complementen
dc.typeArticleen

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