title: Structural homologies of component C5 of human complement with components C3 and C4 by neutron scattering.
abstract: The complement component C5 is one of a family of structurally related plasma proteins that includes components C3 and C4. Activation of C5 is the initial step in the formation of the membrane attack complex of complement. Analysis of the solution structure of C5 and comparisons with similar analyses of the structures of C3 and C4 are reported here. Neutron solution scattering gave an Mr for C5 of 201,000, which demonstrates that C5 is monomeric in solution. The radius of gyration RG of C5 at infinite contrast is 4.87 nm and corresponds to an elongated structure. The longest length of C5 was determined to be at least 15-16 nm from three calculations on the basis of the RG, the scattering intensity at zero angle I(0), and the indirect transformation of the scattering curve into real space. Comparison of the RG and contrast variation data and indirect transformations of the scattering curves for C3, C4, and C5 show that these have very similar structures. Comparisons of the C5 scattering curve with Debye small-sphere models previously employed for C4 and C3 show that good curve fits could be obtained. Unlike previous studies that have suggested significant differences, these experiments indicate that, while C5 differs from C3 and C4 in its activation and inactivation pathways, significant structural homology exists between the native proteins, as might be predicted from their high (and similar) sequence homology.
authors.affiliation: Department of Biochemistry and Chemistry, Royal Free Hospital School of Medicine, London, U.K.
authors.forename: S J
authors.initials: SJ
authors.lastname: Perkins
authors.forename: K F
authors.initials: KF
authors.lastname: Smith
authors.forename: A S
authors.initials: AS
authors.lastname: Nealis
authors.forename: P J
authors.initials: PJ
authors.lastname: Lachmann
authors.forename: R A
authors.initials: RA
authors.lastname: Harrison
mesh_terms: D003176:Complement C3 / Q000235:genetics*; D003181:Complement C4 / Q000235:genetics*; D003182:Complement C5 / Q000235:genetics*; D004577:Electron Probe Microanalysis / Q000379:methods; D006801:Humans; D009502:Neutrons; D012689:Sequence Homology, Nucleic Acid
chemical_list: D003176:Complement C3; D003181:Complement C4; D003182:Complement C5