title: Structure of the C3b binding site of CR1 (CD35), the immune adherence receptor.
abstract: Complement receptor type 1 (CR1 or CD35) is a multiple modular protein that mediates the immune adherence phenomenon, a fundamental event for destroying microbes and initiating an immunological response. It fulfills this role through binding C3b/C4b-opsonized foreign antigens. The structure of the principal C3b/C4b binding site (residues 901-1095) of CR1 is reported, revealing three complement control protein modules (modules 15-17) in an extended head-to-tail arrangement with flexibility at the 16-17 junction. Structure-guided mutagenesis identified a positively charged surface region on module 15 that is critical for C4b binding. This patch, together with basic side chains of module 16 exposed on the same face of CR1, is required for C3b binding. These studies reveal the initial structural details of one of the first receptor-ligand interactions to be identified in immunobiology.
authors.affiliation: Edinburgh Protein Interaction Centre, Joseph Black Chemistry Building, University of Edinburgh, West Mains Road, Edinburgh EH9 3JR, United Kingdom.
authors.forename: Brian O
authors.initials: BO
authors.lastname: Smith
authors.forename: Rosie L
authors.initials: RL
authors.lastname: Mallin
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Krych-Goldberg
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.forename: Richard E
authors.initials: RE
authors.lastname: Hauhart
authors.forename: Krystyna
authors.initials: K
authors.lastname: Bromek
authors.forename: Dusan
authors.initials: D
authors.lastname: Uhrin
authors.forename: John P
authors.initials: JP
authors.lastname: Atkinson
authors.forename: Paul N
authors.initials: PN
authors.lastname: Barlow
mesh_terms: D001665:Binding Sites; D003179:Complement C3b / Q000378:metabolism*; D006801:Humans; D007104:Immune Adherence Reaction; D009682:Magnetic Resonance Spectroscopy; D016296:Mutagenesis; D017434:Protein Structure, Tertiary; D017463:Receptors, Complement 3b / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D017463:Receptors, Complement 3b; D003179:Complement C3b