PMID: 12743029

 

    Legend: Sugar

Title : Crystal structure of the CUB1- EGF-CUB2 region of mannose-binding protein associated serine protease-2

Abstract :

1. Serum mannose-binding proteins ( MBPs ) are C-type lectins that recognize cell surface carbohydrate structures on pathogens, and trigger killing of these targets by activating the complement pathway
2. MBPs circulate as a complex with MBP-associated serine proteases (MASPs), which become activated upon engagement of a target cell surface
3. The minimal functional unit for complement activation is a MASP homodimer bound to two MBP trimeric subunits
4. MASPs have a modular structure consisting of an N-terminal CUB domain , a Ca(2 +)-binding EGF-like domain , a second CUB domain , two complement control protein modules and a C-terminal serine protease domain
5. The CUB1- EGF-CUB2 region mediates homodimerization and binding to MBP
6. The crystal structure of the MASP-2 CUB1- EGF-CUB2 dimer reveals an elongated structure with a prominent concave surface that is proposed to be the MBP-binding site
7. A model of the full six-domain structure and its interaction with MBPs suggests mechanisms by which binding to a target cell transmits conformational changes from MBP to MASP that allow activation of its protease activity