Structural Analysis of Nonapeptides Derived from Elastin

Elastin-derived peptides are released from the extracellular matrix remodeling by numerous proteases and seem to regulate many biological processes, notably cancer progression. The canonical elastin peptide is VGVAPG, which harbors the XGXXPG consensus pattern, allowing interaction with the elastin receptor complex located at the surface of cells. Besides these elastokines, another class of peptides has been identified. This group of bioactive elastin peptides presents the XGXPGXGXG consensus sequence, but the reason for their bioactivity remains unexplained. To better understand their nature and structure-function relationships, herein we searched the current databases for this nonapeptide motif and observed that the XGXPGXGXG elastin peptides define a specific group of tandemly repeated patterns. Further, we focused on four tandemly repeated human elastin nonapeptides, i.e., AGIPGLGVG, VGVPGLGVG, AGVPGLGVG, and AGVPGFGAG. These peptides were analyzed by means of optical spectroscopies and molecular dynamics. Ultraviolet-circular dichroism and Raman spectra are consistent with a mixture of beta-turn, beta-strand, and random-chain secondary elements in aqueous media. Quantitative analysis of their conformations suggested that turns corresponded to half of the total population of structural elements, whereas the remaining half were equally distributed between beta-strand and unordered chains. These distributions were confirmed by molecular dynamics simulations. Altogether, our data suggest that these highly dynamic peptides harbor a type II beta-turn located in their central part. We hypothesize that this structural element could explain their specific bioactivity. SIGNIFICANCE Elastin fragmentation products, the so-called elastin peptides, may exhibit a bioactivity toward normal and tumor cells. This phenomenon depends on the sequence motif they harbor. Although XGXXPG sequence bioactivity is explained by the presence of a type VIII beta-turn allowing interaction with the elastin receptor complex, the structural reasons for XGXPGXGXG-specific activity remain unexplained. Using data mining, we show that elastin nonapeptides define a specific class of tandemly repeated features. Further, spectroscopic and numerical simulations methods suggest the presence of a type II beta-turn in their conformation. This structural element could explain their bioactivity.