The amino acid sequence coded by the rarely expressed exon 26A of human elastin contains a stable beta-turn with chemotactic activity for monocytes.
The structural and biological properties of the amino acid sequence coded by the rarely expressed exon 26A of human elastin were investigated. The C-terminal portion of this sequence, corresponding to residues 600-619 of human tropoelastin, REGDPSSSQHLPSTPSSPRV and three shorter derived peptides, LREGDPSS, SSSQHLPS, and LPSTPSSP, were synthesized and studied. Spectroscopic analyses by CD and NMR have identified a type II beta-turn within the sequence REGD of the octapeptide LREGDPSS. This structural motif was found also in the tetrapeptide REGD in both trifluoroethanol and water. The CD spectrum of the tetrapeptide REGD in trifluoroethanol was consistent with a pure type II beta-turn. A high chemotactic activity for monocytes was exhibited by the structured peptides REGD (CI 0.90 at 10(-)7 M) and LREGDPSS (CI 0.80 at 10(-)11 M), at variance with the unfolded peptides LPSTPSSP and SSSQHLPS, suggesting that this activity is strictly correlated with folded structures. Because the exon 26A of human elastin is expressed in the neointima of hypertensive pulmonary arteries, and macrophages are present in this pathologic tissue [Liptay et al. (1993) J. Clin. Invest. 91, 588-594], the chemotactic activity for human monocytes reported in this paper is consistent with an active role played by the exon 26A in inducing the migration of the monocyte/macrophage cells to the neointima.
Department of Chemistry, University of Basilicata, Potenza, Italy.
F
F
Bisaccia
M A
MA
Castiglione-Morelli
S
S
Spisani
A
A
Ostuni
A
A
Serafini-Fracassini
A
A
Bavoso
A M
AM
Tamburro
D000595:Amino Acid Sequence; D002634:Chemotaxis, Leukocyte; D002942:Circular Dichroism; D004549:Elastin / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D005091:Exons; D015870:Gene Expression; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017433:Protein Structure, Secondary; D013696:Temperature
D009842:Oligopeptides; D004549:Elastin