Human leukocyte elastase hydrolysis of peptides derived from human elastin exon 24.
In normal and pathological tissues, polymorphonuclear leukocyte proteases (elastase, cathepsin G and proteinase 3) may generate soluble peptides through limited proteolysis of elastin, the main component of mature elastic fibres. Elastin-derived peptides display diverse biological activities including cell migration, differentiation, proliferation, chemotaxis, tumor progression and up-regulation of metalloproteinases. To be biologically active, their structures must adopt a beta-turn conformation which accommodates to the cell surface-located elastin binding protein. In this study, we established that human elastin exon 24-derived peptides are hydrolysed by leukocyte elastase, when the active site is fully occupied (from S(5) to S'(3)). As shown by mass spectrometry analyses, a major cleavage site was demonstrated at a Val-Ala bond and a minor one at Gly-Val bond. For longer peptides, the hydrolysed fragments could themselves be re-hydrolysed. If the shortest fragments do not contain the GxxPG sequence known to stimulate cellular effects, some of the intermediates together with hydrolysis fragments generated by other proteases such as proteinase 3, may possess this motif.
Lombard
C
C
Laboratoire de Biochimie Analytique et Synthèse Bioorganique, UFR Chimie-Biochimie, Bâtiment Chevreul, Université Claude Bernard Lyon 1, 43 boulevard du 11 novembre 1918, F-69622 Villeurbanne Cedex, France.
Arzel
L
L
Bouchu
D
D
Wallach
J
J
Saulnier
J
J
D000595:Amino Acid Sequence; D004549:Elastin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005091:Exons / Q000235:genetics*; D006801:Humans; D006868:Hydrolysis; D019272:Leukocyte Elastase / Q000378:metabolism*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*
D009842:Oligopeptides; D010446:Peptide Fragments; D004549:Elastin; C042635:valyl-glycyl-valyl-alanyl-prolyl-glycine; D019272:Leukocyte Elastase