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Structural basis for engagement by complement factor H of C3b on a self surface

DOI: 10.1038/nsmb.2018 DOI Help
PMID: 21317894 PMID Help

Authors: Hugh P. Morgan (University of Edinburgh) , Christoph Q. Schmidt (University of Edinburgh) , Mara Guariento (University of Edinburgh) , Bärbel S. Blaum (University of Edinburgh) , Dominic Gillespie (University of Edinburgh) , Andrew P. Herbert (University of Edinburgh) , David Kavanagh (University of Newcastle upon Tyne) , Haydyn D. T. Mertens (European Molecular Biology Laboratory) , Dmitri I. Svergun (European Molecular Biology Laboratory) , Conny M. Johansson (University of Edinburgh) , Dušsan Uhrín (University of Edinburgh) , Paul N. Barlow (University of Edinburgh) , Jonathan P. Hannan (University of Edinburgh)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Structural & Molecular Biology , VOL 18 (4) , PAGES 463 - 470

State: Published (Approved)
Published: February 2011
Diamond Proposal Number(s): 1225

Abstract: Complement factor H (FH) attenuates C3b molecules tethered by their thioester domains to self surfaces and thereby protects host tissues. Factor H is a cofactor for initial C3b proteolysis that ultimately yields a surface-attached fragment (C3d) corresponding to the thioester domain. We used NMR and X-ray crystallography to study the C3d–FH19–20 complex in atomic detail and identify glycosaminoglycan-binding residues in factor H module 20 of the C3d–FH19–20 complex. Mutagenesis justified the merging of the C3d–FH19–20 structure with an existing C3b–FH1–4 crystal structure. We concatenated the merged structure with the available FH6–8 crystal structure and new SAXS-derived FH1–4, FH8–15 and FH15–19 envelopes. The combined data are consistent with a bent-back factor H molecule that binds through its termini to two sites on one C3b molecule and simultaneously to adjacent polyanionic host-surface markers.

Journal Keywords: Complement; Complement; Crystallography; X-Ray; Models; Molecular; Mutagenesis; Nuclear; Biomolecular; Protein Conformation

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography