Localization and characterization of the Mannose-Binding Lectin (MBL)-associated-serine protease-2 binding site in rat ficolin-A: Equivalent binding sites within the collagenous domains of MBLs and ficolins

Date

2007-07

Advisors

Journal Title

Journal ISSN

ISSN

Volume Title

Publisher

The American Association of Immunologists

Type

Article

Peer reviewed

Yes

Abstract

Ficolins and mannose-binding lectins (MBLs) are the first components of the lectin branch of the complement system. They comprise N-terminal collagen-like domains and C-terminal pathogen-recognition domains (fibrinogen-like domains in ficolins and C-type carbohydrate-recognition domains in MBLs), which target surface-exposed N-acetyl groups or mannose-like sugars on microbial cell walls. Binding leads to activation of MBL-associated serine protease-2 (MASP-2) to initiate complement activation and pathogen neutralization. Recent studies have shown that MASP-2 binds to a short segment of the collagen-like domain of MBL. However, the interaction between ficolins and MASP-2 is relatively poorly understood. In this study, we show that the MASP-2 binding site on rat ficolin-A is also located within the collagen-like domain and encompasses a conserved motif that is present in both MBLs and ficolins. Characterization of this motif using site-directed mutagenesis reveals that a lysine residue in the X position of the Gly-X-Y collagen repeat, Lys(56) in ficolin-A, which is present in all ficolins and MBLs known to activate complement, is essential for MASP-2 binding. Adjacent residues also make important contributions to binding as well as to MASP activation probably by stabilizing the local collagen helix. Equivalent binding sites and comparable activation kinetics of MASP-2 suggest that complement activation by ficolins and MBLs proceeds by analogous mechanisms.

Description

Keywords

ficolin-A, MASP

Citation

Venkatraman Girija, U., Dodds, A.W., Roscher, S., Reid, K.B. and Wallis, R. (2007) Localization and characterization of the Mannose-Binding Lectin (MBL)-associated-serine protease-2 binding site in rat ficolin-A: Equivalent binding sites within the collagenous domains of MBLs and ficolins. The Journal of Immunology, 179 (1), pp. 455-462

Rights

Research Institute

Institute for Allied Health Sciences Research