Publication
Article Metrics
Citations
Online attention
Structural basis for engagement by complement factor H of C3b on a self surface
DOI:
10.1038/nsmb.2018
PMID:
21317894
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)
,
Dusan
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
Discipline Tags:
Technical Tags: