The action of MBL-associated serine protease 1 (MASP1) on factor XIII and fibrinogen

Anders Krarup, Krishana C. Gulla, P. Gál, Krishnan Hajela, Robert B. Sim

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

The complement system is an important recognition and effector mechanism of the innate immune system that upon activation leads to the elimination of foreign bodies. It can be activated through three pathways of which the lectin pathway is one. The lectin pathway relies on the binding of mannan-binding lectin (MBL) or the ficolins and the subsequent activation of the MBL-associated serine proteases (MASPs), namely, MASP1, 2 and 3 which all form complexes with both MBL and the ficolins. Major substrates have only been identified for MASP2 i.e. C4 and C2. For MASP1 only a few protein substrates which are cleaved at a low rate have been identified while none are known for MASP3. Since chromogenic substrate screenings have shown that MASP1 has thrombin-like activity, we wanted to investigate the catalytic potential of MASP1 towards two major proteins involved in the clotting process, fibrinogen and factor XIII, and compare the activity directly with that of thrombin. We found that rMASP1 and thrombin cleave factor XIII A-chain and the fibrinogen β-chain at identical sites, but differ in cleavage of the fibrinogen α-chain. The thrombin turnover rate of factor XIII is approximately 650 times faster than that of rMASP1 at 37°C, pH 7.4. rMASP1 cleavage of fibrinogen leads to the release of the proinflammatory peptide fibrinopeptide B. Thus rMASP1 has similar, but not identical specificity to thrombin and its catalytic activity for factor XIII and fibrinogen cleavage is much lower than that of thrombin. Nevertheless, rMASP1 can drive the formation of cross-linked fibrinogen. Since MASP1 is activated on contact of MBL or the ficolins with microorganisms, fibrinogen and factor XIII may be involved in the elimination of invading pathogens.

Original languageEnglish
Pages (from-to)1294-1300
Number of pages7
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1784
Issue number9
DOIs
Publication statusPublished - Sep 2008

Fingerprint

Mannose-Binding Protein-Associated Serine Proteases
Mannose-Binding Lectin
Factor XIII
Serine Proteases
Fibrinogen
Thrombin
Lectins
Fibrinopeptide B
Chemical activation
Chromogenic Compounds
Immune system
Pathogens
Substrates
Foreign Bodies
Microorganisms
Immune System
Catalyst activity
Screening
Proteins
Peptides

Keywords

  • Coagulation system
  • Complement
  • Factor XIII
  • Fibrinogen
  • Lectin pathway
  • MASP

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Analytical Chemistry
  • Molecular Biology
  • Medicine(all)

Cite this

The action of MBL-associated serine protease 1 (MASP1) on factor XIII and fibrinogen. / Krarup, Anders; Gulla, Krishana C.; Gál, P.; Hajela, Krishnan; Sim, Robert B.

In: Biochimica et Biophysica Acta - Proteins and Proteomics, Vol. 1784, No. 9, 09.2008, p. 1294-1300.

Research output: Contribution to journalArticle

Krarup, Anders ; Gulla, Krishana C. ; Gál, P. ; Hajela, Krishnan ; Sim, Robert B. / The action of MBL-associated serine protease 1 (MASP1) on factor XIII and fibrinogen. In: Biochimica et Biophysica Acta - Proteins and Proteomics. 2008 ; Vol. 1784, No. 9. pp. 1294-1300.
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