A 2D IR Study of Isotope-Edited Variants of the Elastin-like GVGVPGVG Peptide and the Size Dependent Behavior of (VPGVG)n

TL;DR

This study employs isotope-edited 2D IR spectroscopy combined with spectral modeling to identify dominant turn conformations in elastin-like peptides, revealing stable structures across various conditions and elucidating their size-dependent behavior.

Contribution

It introduces a novel application of isotope-edited 2D IR spectroscopy to characterize transient conformations in disordered elastin-like peptides, advancing understanding of their structural dynamics.

Findings

Peptides exhibit high populations of durable turn structures.

Turn conformations are consistent across temperature and salt variations.

Larger peptides maintain significant turn populations, indicating size-dependent behavior.

Abstract

This study uses two-dimensional infrared (2D IR) spectroscopy in conjunction with isotope labeling and spectral modeling from molecular dynamics simulations to identify the dominant turn conformations that exist in equilibrium ensembles of the (VPGVG)n family of intrinsically disordered elastin-like peptides. Numerous models have been proposed to explain the origins of elastin's elasticity and its counterintuitive ability to become structured upon heating. However, the structure of elastin remains unassigned because none of the techniques currently used to study highly disordered amino acid sequences have a time resolution that is faster than the lifetime of a transient conformation in a disordered sequence. Because these conformations exchange on time scales longer than the 5-6 ps required for 2D IR measurements, isotope-edited 2D IR spectroscopy was chosen to study this family of peptides. This study first examined the small GVGVPGVG peptide at a series of temperatures and salt concentrations to assign its dominant turn conformations and to determine what variables alter the populations of these conformations. These data were then used to identify the dominant turn conformations that exist in larger elastin-like peptides including (GVGVP)251. The results indicate that the (VPGVG)n family of elastin-like peptides contain a high population of both an irregular turn structure with 2 peptide-peptide hydrogen bonds to the proline amide C=O group and a conventional turn structure with 1 peptide-peptide hydrogen bond to the proline amide C=O group. These turn structures are durable, showing a significant population of closed turns at all temperatures and salt concentrations studied.