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

TY - GEN

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

AU - Kjaer, Troels R

AU - Thiel, Steffen

AU - Andersen, Gregers R

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

PY - 2013/12/15

Y1 - 2013/12/15

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.

KW - Animals

KW - Complement Activation

KW - Complement C4

KW - Complement Pathway, Mannose-Binding Lectin

KW - Complement System Proteins

KW - Humans

KW - Mannose-Binding Protein-Associated Serine Proteases

U2 - 10.1016/j.molimm.2013.05.220

DO - 10.1016/j.molimm.2013.05.220

M3 - Conference article

C2 - 23810291

SN - 0161-5890

VL - 56

SP - 222

EP - 231

JO - Molecular Immunology

JF - Molecular Immunology

IS - 3

T2 - 14th European Meeting on Complement in Human Disease

Y2 - 17 August 2013 through 21 August 2013

ER -