Published in
American Association for the Advancement of Science, Science, 6012(330), p. 1816-1820, 2010
Links
- ORCID
- ORCID
- American Association for the Advancement of Science
- [www.ncbi.nlm.nih.gov] | PDF
- [www.researchgate.net] | PDF
- [www.ncbi.nlm.nih.gov] | PDF
- [www.ncbi.nlm.nih.gov] | PDF
- [citeseerx.ist.psu.edu] | PDF
- [complement.us] | PDF
- [europepmc.org] | PDF
Tools
Structures of C3b in Complex with Factors B and D Give Insight into Complement Convertase Formation
,
Daniel Ricklin ,
Jin Wu,
Apostolia Tzekou,
Rachel S. Wallace,
John D. Lambris,
Piet Gros
Full text: Download
Abstract
Activation of the complement cascade induces inflammatory responses and marks cells for immune clearance. In the central complement-amplification step, a complex consisting of surface-bound C3b and factor B is cleaved by factor D to generate active convertases on targeted surfaces. We present crystal structures of the pro-convertase C3bB at 4 angstrom resolution and its complex with factor D at 3.5 angstrom resolution. Our data show how factor B binding to C3b forms an open “activation” state of C3bB. Factor D specifically binds the open conformation of factor B through a site distant from the catalytic center and is activated by the substrate, which displaces factor D’s self-inhibitory loop. This concerted proteolytic mechanism, which is cofactor-dependent and substrate-induced, restricts complement amplification to C3b-tagged target cells.