Studies on Cross-Linked Regions of Elastin

Abstract

Elastin, a protein of unique elasticity and tensile strength, is a connective tissue component. Like most elastomers, it consists of randomly coiled polymer chains, joined together by cross-links into an extensible, three dimensional network. The major cross-links of elastin are formed as the result of the deamination of three out of four lysine side chains which subsequently condense to give desmosine or isodesmosine cross-links. We made a novel use of Edman degradation in the study of desmosine and isodesmosine containing elastolytic peptides of mature elastin. This permitted the isolation and sequence studies of peptides C-terminal to the desmosine cross-links in bovine, porcine and human aortic elastin as well as bovine ligamentum nuchae elastin. This identifies the lysines in the tropoelastin (soluble precursor of elastin) which give rise to the desmosine cross-links. The sequences of the C-terminal peptides were found to fall into two distinct classes, one starting with hydrophobic residues, the other starting with alanine. The study of lysine sequences of tropoelastin from a lathyritic calf, with the use of Myxobacter AL-I Protease II, suggests that essentially all lysines occur in pairs separated by two or three small amino acid residues. The majority of the lysines occur in the sequence -Lys-Ala-Ala-Lys-and -Lys-Ala-Ala-Ala-Lys-. It is proposed that two such pairs meet to form desmosine or isodesmosine cross-link and that the hydrophobic residue at the carboxyl end of lysine prevents the enzymic oxidative deamination of the adjacent lysine 6-amino group and this then contributes the nitrogen to the pyridinium ring of the cross-link.