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



