Structural characterization of human elastin derived peptides containing the GXXP sequence

✍ Scribed by Gautier Moroy; Alain J. P. Alix; Stéphanie Héry-Huynh

• Publisher: Wiley (John Wiley & Sons)
• Year: 2005
• Tongue: English
• Weight: 209 KB
• Volume: 78
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.20276

✦ Synopsis

Abstract

The degradation of elastin, the insoluble biopolymer of tropoelastin, can lead to the production of small peptides. These elastin‐derived peptides (EDPs) are playing a key role in cellular behavior within the extracellular matrix, showing a great variety of biological effects such as chemotaxis, stimulation of cell proliferation, ion flux modifications, vasorelaxation, and inflammatory enzymes secretion. It has also been demonstrated recently that EDPs containing the GXXPG motif could induce pro‐MMP1 and pro‐MMP3 upregulation. Elastolysis could then cause collagen degradation and play an important role in the aging process. Many experimental studies have been devoted to EDPs, but their structure/activity relationships are not well elucidated yet. However, the assumption that their active conformation is a type VIII β‐turn on GXXP was highly suggested on the basis of predictive statistical calculations.

Investigation of the EDPs three‐dimensional (3D) structure would provide useful information for drug‐design strategies to propose specific inhibitors. The work presented here reports theoretical results obtained from molecular dynamics simulations performed over 128 human EDPs containing the GXXP motif. We show that all the peptides, for which the central residues are not glycines, adopt a canonical (or very close to) type VIII β‐turn structure on the GXXP sequence. Amino acids surrounding this motif are also important for the structural behavior. Any residue located before the GXXP motif (XGXXP) increases the β‐turn stabilization, whereas the residue located after GXXP (GXXPX) has no significant structural effect. Moreover, we show their biological activity can be correlated with their ability to exhibit a type VIII β‐turn conformation. © 2005 Wiley Periodicals, Inc. Biopoly 78: 206–220, 2005