Investigating the role of (2S,4R)-4-hydroxyproline in elastin model peptides

TY - JOUR

T1 - Investigating the role of (2S,4R)-4-hydroxyproline in elastin model peptides

AU - Bochicchio, Brigida

AU - Laurita, Alessandro

AU - Heinz, Andrea

AU - Schmelzer, Christian E H

AU - Pepe, Antonietta

PY - 2013/12/9

Y1 - 2013/12/9

N2 - Post-translational modifications play a key role in defining the biological functions of proteins. Among them, the hydroxylation of proline producing the (2S,4R)-4-hydroxyproline (Hyp) is one of the most frequent modifications observed in vertebrates, being particularly abundant in the proteins of the extracellular matrix. In collagen, hydroxylation of proline plays a critical role, conferring the correct structure and mechanical strength to collagen fibers. In elastin, the exact role of this modification is not yet understood. Here we show that Hyp-containing elastin polypeptides have flexible molecular structures, analogously to proline-containing polypeptides. In turn, the self-assembly of the elastin peptides is significantly altered by the presence of Hyp, evidencing different supramolecular structures. Also the in vitro susceptibility to protease digestion is changed. These findings give a better insight into the elastic fiber formation and degradation processes in the extracellular matrix. Furthermore, our results could contribute in defining the subtle role of proline structural variants in the folding and self-assembly of elastin-inspired peptides, helping the rational design of elastin biomaterials.

AB - Post-translational modifications play a key role in defining the biological functions of proteins. Among them, the hydroxylation of proline producing the (2S,4R)-4-hydroxyproline (Hyp) is one of the most frequent modifications observed in vertebrates, being particularly abundant in the proteins of the extracellular matrix. In collagen, hydroxylation of proline plays a critical role, conferring the correct structure and mechanical strength to collagen fibers. In elastin, the exact role of this modification is not yet understood. Here we show that Hyp-containing elastin polypeptides have flexible molecular structures, analogously to proline-containing polypeptides. In turn, the self-assembly of the elastin peptides is significantly altered by the presence of Hyp, evidencing different supramolecular structures. Also the in vitro susceptibility to protease digestion is changed. These findings give a better insight into the elastic fiber formation and degradation processes in the extracellular matrix. Furthermore, our results could contribute in defining the subtle role of proline structural variants in the folding and self-assembly of elastin-inspired peptides, helping the rational design of elastin biomaterials.

KW - Amino Acid Sequence

KW - Animals

KW - Circular Dichroism

KW - Humans

KW - Hydroxylation

KW - Hydroxyproline

KW - Magnetic Resonance Spectroscopy

KW - Microscopy, Atomic Force

KW - Microscopy, Electron, Transmission

KW - Molecular Sequence Data

KW - Nanofibers

KW - Peptide Fragments

KW - Protein Processing, Post-Translational

KW - Protein Structure, Secondary

KW - Tropoelastin

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1021/bm4011529

DO - 10.1021/bm4011529

M3 - Journal article

C2 - 24127724

SN - 1525-7797

VL - 14

SP - 4278

EP - 4288

JO - Biomacromolecules

JF - Biomacromolecules

IS - 12

ER -