3POJ

Crystal structure of MASP-1 CUB2 domain bound to Ethylamine

Summary for 3POJ

• Entry DOI: 10.2210/pdb3poj/pdb
• Related: 3POB 3POF
• Descriptor: Mannan-binding lectin serine protease 1, CALCIUM ION, ETHANAMINE, ... (6 entities in total)
• Functional Keywords: cub domain, ca2+ binding site, complex with ethylamine, complement protein, lectin pathway of complement, mbl, mbp, ficolins, bloodstream, hydrolase
• Biological source: Rattus norvegicus (brown rat,rat,rats)
• Cellular location: Secreted: Q8CHN8
• Total number of polymer chains: 2
• Total formula weight: 26622.53

Authors

Gingras, A.R.,Moody, P.C.E.,Wallis, R. (deposition date: 2010-11-22, release date: 2011-08-24, Last modification date: 2023-09-06)

Primary citation

Gingras, A.R.,Girija, U.V.,Keeble, A.H.,Panchal, R.,Mitchell, D.A.,Moody, P.C.,Wallis, R.
Structural Basis of Mannan-Binding Lectin Recognition by Its Associated Serine Protease MASP-1: Implications for Complement Activation.
Structure, 19:1635-1643, 2011

PubMed 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.

PubMed: 22078562
DOI: 10.1016/j.str.2011.08.014

Experimental method

X-RAY DIFFRACTION (1.451 Å)