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Title: Structural basis of mannan-binding lectin recognition by its associated serine protease MASP-1: implications for complement activation.
Authors: Gingras, AR
Girija, UV
Keeble, AH
Panchal, R
Mitchell, DA
Moody, PC
Wallis, R
First Published: 9-Nov-2011
Citation: STRUCTURE, 2011, 19 (11), pp. 1635-1643
Abstract: Complement 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.
DOI Link: 10.1016/j.str.2011.08.014
eISSN: 1878-4186
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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