Structural Basis of Mannan-Binding Lectin Recognition by Its Associated Serine Protease MASP-1: Implications for Complement Activation
Gingras, Alexandre R., Girija, Umakhanth Venkatraman, Keeble, Anthony H., Panchal, Roshni, Mitchell, Daniel Anthony, Moody, Peter C. E. and Wallis, Russell. (2011) Structural Basis of Mannan-Binding Lectin Recognition by Its Associated Serine Protease MASP-1: Implications for Complement Activation. Structure, Vol.19 (No.11). pp. 1635-1643. ISSN 0969-2126Full text not available from this repository.
Official URL: http://dx.doi.org/10.1016/j.str.2011.08.014
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.
|Item Type:||Journal Article|
|Subjects:||R Medicine > R Medicine (General)|
|Divisions:||Faculty of Medicine > Warwick Medical School|
|Journal or Publication Title:||Structure|
|Number of Pages:||9|
|Page Range:||pp. 1635-1643|
|Access rights to Published version:||Restricted or Subscription Access|
Actions (login required)