title: Solution structure of a functionally active fragment of decay-accelerating factor.
abstract: The second and third modules of human decay accelerating factor (DAF) are necessary and sufficient to accelerate decay of the classical pathway (CP) convertase of complement. No structure of a mammalian protein with decay-accelerating activity has been available to date. We therefore determined the solution structure of DAF modules 2 and 3 (DAF approximately 2,3). Structure-guided analysis of 24 mutants identified likely contact points between DAF and the CP convertase. Three (R96, R69, and a residue in the vicinity of L171) lie on DAF approximately 2,3's concave face. A fourth, consisting of K127 and nearby R100, is on the opposite face. Regions of module 3 remote from the semiflexible 2-3 interface seem not to be involved in binding to the CP convertase. DAF thus seems to occupy a groove on the CP convertase such that both faces of DAF close to the 2-3 junction (including a positively charged region that encircles the protein at this point) interact simultaneously. Alternative pathway convertase interactions with DAF require additional regions of CCP 3 lying away from the 2-3 interface, consistent with the established additional requirement of module 4 for alternative pathway regulation.
authors.affiliation: Edinburgh Protein Interaction Centre, University of Edinburgh, Edinburgh EH9 3JJ, Scotland.
authors.forename: Stanislava
authors.initials: S
authors.lastname: Uhrinova
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.forename: Graeme
authors.initials: G
authors.lastname: Ball
authors.forename: Krystyna
authors.initials: K
authors.lastname: Bromek
authors.forename: Dusan
authors.initials: D
authors.lastname: Uhrin
authors.forename: M Edward
authors.initials: ME
authors.lastname: Medof
authors.forename: Paul N
authors.initials: PN
authors.lastname: Barlow
mesh_terms: D001665:Binding Sites; D018958:CD55 Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012996:Solutions; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D018958:CD55 Antigens; D010446:Peptide Fragments; D011994:Recombinant Proteins; D012996:Solutions; D050577:Complement C3-C5 Convertases