Amino acid sequence and sequence variability of the amino-terminal regions of lysine-rich histones.

The amino acid sequence has been determined for the first 72 residues of a lysine-rich histone from rabbit thymus. These are the residues contained in a fragment released from the histone by treatment with N-bromosuccinimide. Peptides derived by tryptic, thermolysin, and chymotryptic digestion of this 72-residue fragment were used to reconstruct the total sequence. Analysis of the sequence revealed some unusual aspects of the structure of the fragment, which comprises about onethird of the histone molecule. Thirty of the first 40 residues are accounted for by lysine, alanine, and proline; this portion of the fragment includes sequences of 4,2, and 3 consecutive basic residues. The last 32 residues contain all the hydrophobic amino acids (valine, isoleucine, leucine, tyrosine) of the fragment but have few basic residues and no prolines. The NH2 terminus of the histone is acetylated. Comparison of the sequence of the NHz-terminal half of this lysine-rich histone with the entire sequences of the slightly lysine-rich and arginine-rich histones shows that all three have similar characteristics, that is, an NHz-terminal region rich in basic amino acids and a COOH-terminal portion rich in hydrophobic residues. Tryptic peptides from the NHz-terminal N-bromosuccinimide fragment of two other thymus lysine-rich histones have been isolated. These peptides (with partial sequences) were aligned by direct identity or analogy with the complete amino acid sequence of the NH%-terminal N-bromosuccinimide fragment of the lysine-rich histone studied previously. It was found that there were from 7 to 14 amino acid differences between fractions. One of the amino acid interchanges eliminates a major phosphorylation site.