Primary structure of human C-reactive protein.

The complete amino acid sequence has been derived for human C-reactive protein (CRP). The protein yielded a unique sequence containing 187 amino acids in a single polypeptide chain. The NH2-terminal residue of CRP is pyrrolidonecarboxylic acid and the COOH terminus is proline. The 2 half-cystine residues at positions 36 and 78 are involved in a disulfide bond. Based on the amino acid composition derived from the sequence data, a minimal molecular weight of 20,946 has been calculated for human CRP. This value agrees well with the molecular weight of 21,500 established by gel filtration of CRP in 5.0 M guanidine Cl (Gotschlich, E.C., and Edelman, G.M. (1965) Proc. Natl. Acad. Sci. U.S.A. 54, 558--566). The primary structure of human CRP has been examined for internal homology and compared to all known proteins whose structures were published before April, 1978 by two computer programs; program SEARCH and program RELATE (Dayhoff, M. O., ed (1976) in Atlas of Protein Sequence and Structure, Vol. 5, Suppl. 2, pp. 3--8, National Biomedical Research Foundation, Silver Spring, MD). The computer analyses showed no significant repeating sequences within the C-reactive protein molecule. This observation seems to rule out the possibility of gene duplication in the evolution of this protein. Distant homologies, which were statistically insignificant, have been noted to the CH2 domain of immunoglobulin G (IgG) and to C3a anaphylotoxin. The homologie noted are insufficient to support a common evolutionary origin of these proteins. No homology region in other heavy chains was observed. It is therefore preferable, at this point in time, to assign CRP and the protein known as 9.5 S alpha-glycoprotein, P component, and Clt to a new super family unrelated to any other proteins investigated. The homology between these proteins was demonstrated previously (Osmand, A.P., Friedenson, B., Gewurz, H., Painter, R.H., Hofmann, T., and Shelton, E. (1977) Proc. Natl. Acad. Sci. U.S.A. 74, 739--743) on the basis of sequence data on approximately 20 NH2-terminal residues of rabbit C-reactive protein, of Clt, and a cyanogen bromide fragment of human CRP.