3pog

From Proteopedia

Crystal structure of the MASP-1 CUB2 domain bound to Ca2+

Structural highlights

3pog is a 3 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.749Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MASP1_RAT Functions in the lectin pathway of complement, which performs a key role in innate immunity by recognizing pathogens through patterns of sugar moieties and neutralizing them. The lectin pathway is triggered upon binding of mannan-binding lectin (MBL) and ficolins to sugar moieties which leads to activation of the associated proteases MASP1 and MASP2. Functions as an endopeptidase and may activate MASP2 or C2 or directly activate C3 the key component of complement reaction. Isoform 2 may have an inhibitory effect on the activation of the lectin pathway of complement or may cleave IGFBP5 (By similarity).

Publication Abstract from PubMed

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.

Structural Basis of Mannan-Binding Lectin Recognition by Its Associated Serine Protease MASP-1: Implications for Complement Activation.,Gingras AR, Girija UV, Keeble AH, Panchal R, Mitchell DA, Moody PC, Wallis R Structure. 2011 Nov 9;19(11):1635-43. PMID:22078562^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gingras AR, Girija UV, Keeble AH, Panchal R, Mitchell DA, Moody PC, Wallis R. Structural Basis of Mannan-Binding Lectin Recognition by Its Associated Serine Protease MASP-1: Implications for Complement Activation. Structure. 2011 Nov 9;19(11):1635-43. PMID:22078562 doi:10.1016/j.str.2011.08.014