Stoichiometry of complexes between mannose-binding protein and its associated serine proteases. Defining functional units for complement activation

J Biol Chem. 2001 Jul 13;276(28):25894-902. doi: 10.1074/jbc.M103539200. Epub 2001 May 3.

Abstract

Serum mannose-binding protein (MBP) initiates the lectin branch of the complement cascade by binding to sugars on the surfaces of microorganisms and activating two MBP-associated serine proteases (MASP-1 and MASP-2). Rat serum MBP consists of oligomers containing up to four copies of a subunit that is composed of three identical polypeptide chains. Biophysical analysis of intact and truncated MASPs indicates that each MASP is a homodimer that is stabilized through interactions involving an N-terminal CUB domain. The binding sites for MBP are formed from the three N-terminal MASP domains, in which two CUB modules interact with MBP. Each MASP dimer contains binding sites for two MBP subunits. Both sites must be occupied by subunits from a single MBP oligomer to form a stable complex. Thus, the smallest functional unit for complement activation consists of MBP dimers bound to MASP-1 or MASP-2 homodimers. Trimers and tetramers of MBP form complexes containing up to two MASPs. The results reveal how MASP-1 and MASP-2 can function independently to activate the complement cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / chemistry*
  • Collectins
  • Protein Binding
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Serine Endopeptidases / chemistry*

Substances

  • Carrier Proteins
  • Collectins
  • Recombinant Proteins
  • Serine Endopeptidases