Complete amino acid sequence of a 50,000-dalton fragment of human ceruloplasmin.

Abstract

The complete amino acid sequence was determined for a 50,000-dalton fragment that is an internal segment of the single polypeptide chain of human [plasma] ceruloplasmin [ferroxidase; iron (II):oxygen oxidoreductase, EC 1.16.3.1]. The fragment (designated Cp F4) contains 405 amino acid residues, has 1 glucosamine-containing carbohydrate unit and, together with the 19,000-dalton fragment that follows it, accounts for the carboxyl-terminal half of the molecule. Fragment Cp F4 has a very nonuniform distribution of certain amino acid residues, which show a high potential to be adjacent to or 1 residue separated from a similar amino acid. This is most pronounced for acid and amide residues (65% clustered), aromatic residue (56% clustered) and basic residues (41% clustered). There is a long-range clustering of proline residues at the amino- and carboxyl-terminal 60 residues (50% clustered). There are a number of short repeated segments of sequence. Calculations based on parameters predictive of secondary structure folding patterns indicate that the 50,000-dalton fragment has a low content of .alpha.-helix and is predominantly .beta.-sheet, .beta.-turn and random in structure. Limited enzymatic cleavage of human ceruloplasmin to yield 67,000, 50,000 and 19,000 dalton fragments occurs at specific exposed sites of random structure in between domain-like regions.