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| Subject Categories: Structural Biology | Immunology |
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| The EMBO Journal
(2003) 22, 2348–2359, doi:10.1093/emboj/cdg236 |
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| Crystal structure of the CUB1-EGF-CUB2 region of mannose-binding protein associated serine protease-2 |
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| Hadar Feinberg1, 3, Joost C.M. Uitdehaag2, 3, Jason M. Davies1, Russell Wallis2, Kurt Drickamer2 and William I. Weis2 |
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1 Departments of Structural Biology and of Molecular and Cellular Physiology, Stanford University School of Medicine, 299 Campus Drive West, Stanford, CA 94305-5126, USA 2 Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK 3 H.Feinberg and J.C.M.Uitdehaag contributed equally to this work To whom correspondence should be addressed William I. Weis, bill.weis@stanford.edu Received 28 January 2003; Revised 18 March 2003; Accepted 19 March 2003. |
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| Abstract |
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| 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 Ca2+-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. |
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| Keywords: complement, C1 complex, mannose-binding protein, MASP |
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