A study of the structure of human complement component factor H by Fourier transform infrared spectroscopy and secondary structure averaging methods.
Fourier transform infrared spectroscopy was used to investigate the secondary structure of human complement component factor H in H2O and 2H2O buffers. The spectra show a broad amide I band which after second-derivative calculations is shown to be composed of three components at 1645, 1663, and 1685 cm-1 in H2O and at 1638, 1661, and 1680 cm-1 in 2H2O. The frequencies of these components are consistent with the existence of an extensive antiparallel beta-strand secondary structure. The exchange properties of the amide protons of factor H as measured in 2H2O buffers are rapid and lead to an estimate of NH proton nonexchange that is comparable with those for small globular proteins. Human factor H is constructed from a linear sequence of 20 short consensus repeats with a mean of 61 residues in each one. To investigate the secondary structure further, secondary structure predictions were carried out on the basis of an alignment scheme for 101 sequences for these repeats as found in human factor H and 12 other proteins. These predictions were averaged in order to improve the reliability of the calculations. Both the Robson and the Chou-Fasman methods indicate significant beta-structural contents. Residues 21-51 in the 61-residue repeat show a clear prediction of four strands of beta-structure and four beta-turns. A structural model based on antiparallel beta-strands in the secondary structure is proposed and discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
Perkins
S J
SJ
Department of Biochemistry and Chemistry, Royal Free Hospital School of Medicine, London, U.K.
Haris
P I
PI
Sim
R B
RB
Chapman
D
D
D000595:Amino Acid Sequence; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H; D005583:Fourier Analysis; D006801:Humans; D008432:Mathematical Computing; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013055:Spectrophotometry, Infrared
C493495:CFH protein, human; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H