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Crystal structure of the CUB1‐EGF‐CUB2 region of mannose‐binding protein associated serine protease‐2
Author(s) -
Feinberg Hadar,
Uitdehaag Joost C.M.,
Davies Jason M.,
Wallis Russell,
Drickamer Kurt,
Weis William I.
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg236
Subject(s) - serine protease , complement system , proteases , complement control protein , biology , masp1 , serine , microbiology and biotechnology , mannan binding lectin , protease , mannose , biochemistry , plasma protein binding , protein structure , biophysics , classical complement pathway , lectin , phosphorylation , enzyme , antibody , immunology
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.