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

By Hadar Feinberg, Joost C.M. Uitdehaag, Jason M. Davies, Russell Wallis, Kurt Drickamer and William I. Weis


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. MBPs circulate as a complex with MBP-associated serine proteases (MASPs), which become activated upon engagement of a target cell surface. The minimal functional unit for complement activation is a MASP homodimer bound to two MBP trimeric subunits. 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. The CUB1-EGF-CUB2 region mediates homodimerization and binding to MBP. 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. 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

Topics: Articles
Publisher: Oxford University Press
Year: 2003
DOI identifier: 10.1093/emboj/cdg236
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Provided by: PubMed Central
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