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dc.contributor.authorGingras, A. R.en
dc.contributor.authorVenkatraman Girija, U.en
dc.contributor.authorKeeble, A. H.en
dc.contributor.authorPanchal, R.en
dc.contributor.authorMitchell, D. A.en
dc.contributor.authorMoody, P. C. E.en
dc.contributor.authorWallis, R.en
dc.date.accessioned2015-05-29T10:50:20Z
dc.date.available2015-05-29T10:50:20Z
dc.date.issued2011-11
dc.identifier.citationGingras, A.R., Venkatraman Girija, U., Keeble, A.H., Panchal, R., Mitchell, D.A., Moody, P.C.E. and Wallis R. (2011) Structural basis of mannan-binding lectin recognition by its associated serine protease MASP-1: implications for complement activation. Structure, 19 (11), pp. 1635-1643en
dc.identifier.urihttp://hdl.handle.net/2086/10994
dc.description.abstractComplement activation contributes directly to health and disease. It neutralizes pathogens and stimulates immune processes. Defects lead to immunodeficiency and autoimmune diseases, whereas inappropriate activation causes self-damage. In the lectin and classical pathways, complement is triggered upon recognition of a pathogen by an activating complex. Here we present the first structure of such a complex in the form of the collagen-like domain of mannan-binding lectin (MBL) and the binding domain of its associated protease (MASP-1/-3). The collagen binds within a groove using a pivotal lysine side chain that interacts with Ca(2+)-coordinating residues, revealing the essential role of Ca(2+). This mode of binding is prototypic for all activating complexes of the lectin and classical pathways, and suggests a general mechanism for the global changes that drive activation. The structural insights reveal a new focus for inhibitors and we have validated this concept by targeting the binding pocket of the MASP.en
dc.language.isoenen
dc.publisherScience Directen
dc.subjectMASP-1en
dc.subjectcomplement activationen
dc.titleStructural basis of mannan-binding lectin recognition by its associated serine protease MASP-1: implications for complement activationen
dc.typeArticleen
dc.identifier.doihttp://dx.doi.org/10.1016/j.str.2011.08.014
dc.researchgroupInfectious Disease Research Group
dc.peerreviewedYesen
dc.fundernaen
dc.projectidnaen
dc.researchinstituteInstitute for Allied Health Sciences Researchen


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