Solution structure of the fifth repeat of factor H: a second example of the complement control protein module

Abstract

Modules which share the same consensus sequence are assumed to have common structural features, at the secondary and tertiary level. In order to test the extent of such similarities, it is necessary to examine the structures of several examples from each module family. Recently, the first three-dimensional structure of a complement control protein (CCP) module (the 16th repeat of human factor H, H16) was determined using a combination of two-dimensional NMR and simulated annealing [Norman, D.G., Barlow, P.N., Baron, M., Day, A.J., Sim, R.B., & Campbell, I.D. (1991) J. Mol. Biol. 219, 717-725]. Using the same techniques, the three-dimensional structure of a second CCP module (the 5th repeat of human factor H, H5) has now been determined. The primary sequence of H5 contains 17 residues which are identical and in equivalent position to those in H16. Thirteen of these 17 are part of the consensus sequence. The similarities between the secondary structure of H5 and that of H16 are extensive. This implies that the consensus sequence dictates a particular secondary structure. The tertiary structure of H5, a compact hydrophobic core wrapped in beta-strand and sheet, bears much overall resemblance to that of H16. However, there is a deletion in the first strand of H5, and an insertion in a loop, resulting in slightly shorter overall length. This is associated with a rearrangement of residues within the hydrophobic core. The side chain of the highly conserved Tyr29, which occupies a central position within the core of H16, lies on the periphery of the core of H5.

Identification of Residues within the 727–767 Segment of Human Complement Component C3 Important for Its Interaction with Factor H and with Complement Receptor 1 (CR1, CD35)

“…The rC3(H 2 O) molecules were present as metabolically labeled entities in the KBr-treated COS-1 cell transfection supernatants. The fetal bovine serum employed in the culture medium had been treated with K76-COOH in order to inactivate bovine 2 In Fig. 1 and throughout the text, the standard convention for naming single and multiple mutations is employed.…”

Abnormal Immune Complex Processing and Spontaneous Glomerulonephritis in Complement Factor H-Deficient Mice with Human Complement Receptor 1 on Erythrocytes

“…The regulators of complement activation proteins are composed of short-consensus repeat domains of ∼60 aa, and they are highly related within and between even distant species (4)(5)(6). The functional activities of these family members are attributable to their binding to C4 and C3 products (3,7).…”

The Electrostatic Nature of C3d-Complement Receptor 2 Association

“…Several SCR domains can form chains that are not only part of the complement family, such as CR1, CR2, factor H, and the membrane attack complex, but are also noncomplement family proteins, such as the vaccinia control protein, which structurally resembles CR2 but is composed of four SCRs only. It has been proposed that the flexibility and relative orientation of SCR domains, mediated by the variable length interdomain linker, and by the presence (or absence) of side-by-side packing, mediated by hydrophobic side chains, is important for function (19,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32).…”