Toward a structure-based comprehension of the lectin pathway of complement

Mol Immunol. 2013 Dec;56(4):413-22. doi: 10.1016/j.molimm.2013.05.007. Epub 2013 Aug 1.


To initiate the lectin pathway of complement pattern recognition molecules bind to surface-linked carbohydrates or acetyl groups on pathogens or damaged self-tissue. This leads to activation of the serine proteases MASP-1 and MASP-2 resulting in deposition of C4 on the activator and assembly of the C3 convertase. In addition MASP-3 and the non-catalytic MAp19 and MAp44 presumably play regulatory functions, but the exact function of the MASP-3 protease remains to be established. Recent functional studies have significantly advanced our understanding of the molecular events occurring as activation progresses from pattern recognition to convertase assembly. Furthermore, atomic structures derived by crystallography or solution scattering of most proteins acting in the lectin pathway and two key complexes have become available. Here we integrate the current functional and structural knowledge concerning the lectin pathway proteins and derive overall models for their glycan bound complexes. These models are used to discuss cis- versus trans-activation of MASP proteases and the geometry of C4 deposition occurring on glycans in the lectin pathway.

Keywords: C4; Complement system; MASP; MBL; Pattern recognition; Protease activation; Structural biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Complement C3-C5 Convertases / immunology
  • Complement C3-C5 Convertases / metabolism
  • Complement C4 / immunology
  • Complement C4 / metabolism
  • Complement Factor B
  • Complement Pathway, Mannose-Binding Lectin / immunology*
  • Humans
  • Mannose-Binding Lectin / chemistry
  • Mannose-Binding Lectin / immunology*
  • Mannose-Binding Lectin / metabolism
  • Mannose-Binding Protein-Associated Serine Proteases / chemistry
  • Mannose-Binding Protein-Associated Serine Proteases / immunology*
  • Mannose-Binding Protein-Associated Serine Proteases / metabolism
  • Models, Molecular
  • Protein Binding / immunology
  • Protein Structure, Tertiary


  • Complement C4
  • Mannose-Binding Lectin
  • Complement C3-C5 Convertases
  • MASP1 protein, human
  • MASP2 protein, human
  • Mannose-Binding Protein-Associated Serine Proteases
  • Complement Factor B