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

TY - JOUR

T1 - Toward a structure-based comprehension of the lectin pathway of complement

AU - Kjaer, Troels Rønn

AU - Thiel, Steffen

AU - Andersen, Gregers Rom

N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.

PY - 2013/12/31

Y1 - 2013/12/31

N2 - 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.

AB - 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.

U2 - 10.1016/j.molimm.2013.05.007

DO - 10.1016/j.molimm.2013.05.007

M3 - Journal article

C2 - 23911397

SN - 0161-5890

VL - 56

SP - 413

EP - 422

JO - Molecular Immunology

JF - Molecular Immunology

IS - 4

ER -