title: CRIT peptide interacts with factor B and interferes with alternative pathway activation.
abstract: Complement C2 receptor inhibitor trispanning (CRIT) inhibits the classical pathway (CP) C3 convertase formation by competing with C4b for the binding of C2. The C-terminal 11-amino-acid of the first CRIT-extracellular domain (CRIT-H17) has a strong homology with a sequence in the C4beta chain, which is responsible for the binding of C2. Since the CP and alternative pathway (AP) C3 convertases have many functional and structural similarities, we further investigated the effects of CRIT-H17 on the AP. The factor D-mediated cleavage of factor B (FB) was blocked by CRIT-H17. By ELISA and immunoblot, CRIT-H17 was shown to bind FB. CRIT-H17 had no decay activity on the C3bBb complex as compared to decay-accelerating factor. Binding of CRIT-H17 to FB did not interfere with the assembly of C3bB complex. In a haemolytic assay using C2-deficient serum, CRIT-H17 interfered with AP complement activation.
authors.affiliation: University Hospital Basel, Immunonephrology, Department of Research, Hebelstrasse 20, CH-4031 Basel, Switzerland. 12min@mail.hongkong.com
authors.forename: Kwok-Min
authors.initials: KM
authors.lastname: Hui
authors.forename: Bergljót
authors.initials: B
authors.lastname: Magnadóttir
authors.forename: Jürg A
authors.initials: JA
authors.lastname: Schifferli
authors.forename: Jameel M
authors.initials: JM
authors.lastname: Inal
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D051561:Complement C3 Convertase, Alternative Pathway / Q000187:drug effects*; D011415:Complement Factor B / Q000737:chemistry / Q000276:immunology*; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D017434:Protein Structure, Tertiary
chemical_list: C511181:CRIT-H17 peptide; D002352:Carrier Proteins; D010446:Peptide Fragments; D051561:Complement C3 Convertase, Alternative Pathway; D011415:Complement Factor B