title: Structural basis for engagement by complement factor H of C3b on a self surface.
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.
authors.affiliation: Institute of Structural and Molecular Biology, School of Biological Sciences, King's Buildings, University of Edinburgh, Edinburgh, UK.
authors.forename: Hugh P
authors.initials: HP
authors.lastname: Morgan
authors.forename: Christoph Q
authors.initials: CQ
authors.lastname: Schmidt
authors.forename: Mara
authors.initials: M
authors.lastname: Guariento
authors.forename: Bärbel S
authors.initials: BS
authors.lastname: Blaum
authors.forename: Dominic
authors.initials: D
authors.lastname: Gillespie
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Herbert
authors.forename: David
authors.initials: D
authors.lastname: Kavanagh
authors.forename: Haydyn D T
authors.initials: HD
authors.lastname: Mertens
authors.forename: Dmitri I
authors.initials: DI
authors.lastname: Svergun
authors.forename: Conny M
authors.initials: CM
authors.lastname: Johansson
authors.forename: Dušan
authors.initials: D
authors.lastname: Uhrín
authors.forename: Paul N
authors.initials: PN
authors.lastname: Barlow
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Hannan
mesh_terms: D001665:Binding Sites; D003179:Complement C3b / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017242:Complement Factor H / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D016296:Mutagenesis; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation
chemical_list: D003179:Complement C3b; D017242:Complement Factor H