Short elastin-like peptides exhibit the same temperature-induced structural transitions as elastin polymers: implications for protein engineering

Elastin is a major protein component of the vascular wall and is responsible for its unusual elastic properties. Polymers of its repeating VPGVG sequences have been synthesised and shown to exhibit an inverse temperature transition where, as temperature rises, the polymer collapses from an extended chain to a β-spiral structure with three VPGVG units per turn, each pentamer adopting a type II β-turn conformation. These studies, however, have not established whether the temperature-driven conformational change is an intrinsic property of the individual pentameric sequences or a global, co-operative effect of many pentamers within the β-spiral structure. Here, we examine by circular dichroism the behaviour of elastin-like peptides (VPGVG) n , where n varies between 1 and 5. Remarkably, we find that all lengths of peptide undergo an extended↔β-turn transition with increasing temperature, suggesting that the induction of the β-spiral occurs at the level of single pentameric units. The origin of this effect is a positive Δ S term for the transition. At 35°C, the average transition midpoint temperature, the value of TΔ S is about 15 kcal mol −1. With larger oligomers ( n = 3), there is only a modest rise in Δ S, suggesting that the dominant entropic effect resides within the monomer and that interactions between these units make only a small contribution to the energetics of the transition. Charges at the termini, and residue replacements or additions, regulate the transitions for the short peptides in a manner similar to that observed for the longer polymers. The behaviour of the same peptides in trifluoroethanol and SDS solutions is consistent with formation of the β-turn being driven by interactions between non-polar groups. The significance of this behaviour for the rational design of temperature-induced responses in proteins is discussed.