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Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase.
- Source :
-
Molecular cell [Mol Cell] 2004 Apr 09; Vol. 14 (1), pp. 17-28. - Publication Year :
- 2004
-
Abstract
- The C-terminal fragment, Bb, of factor B combines with C3b to form the pivotal C3-convertase, C3bBb, of alternative complement pathway. Bb consists of a von Willebrand factor type A (vWFA) domain that is structurally similar to the I domains of integrins and a serine protease (SP) domain that is in inactive conformation. The structure of the C3bBb complex would be important in deciphering the activation mechanism of the SP domain. However, C3bBb is labile and not amenable to X-ray diffraction studies. We engineered a disulfide bond in the vWFA domain of Bb homologous to that shown to lock I domains in active conformation. The crystal structures of Bb(C428-C435) and its inhibitor complexes reveal that the adoption of the "active" conformation by the vWFA domain is not sufficient to activate the C3-convertase catalytic apparatus and also provide insights into the possible mode of C3-convertase activation.
- Subjects :
- Animals
Binding Sites
Complement C3 Convertase, Alternative Pathway
Complement C3b genetics
Complement Inactivator Proteins metabolism
Crystallography, X-Ray
Disulfides chemistry
Elapid Venoms metabolism
Enzyme Activation
Enzyme Inhibitors chemistry
Enzyme Inhibitors metabolism
Models, Molecular
Peptide Fragments genetics
Recombinant Proteins chemistry
Recombinant Proteins genetics
Recombinant Proteins metabolism
von Willebrand Factor metabolism
Complement C3-C5 Convertases metabolism
Complement C3b chemistry
Complement C3b metabolism
Complement Pathway, Alternative physiology
Peptide Fragments chemistry
Peptide Fragments metabolism
Protein Conformation
von Willebrand Factor chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1097-2765
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 15068800
- Full Text :
- https://doi.org/10.1016/s1097-2765(04)00160-1