Introduction of Temperature-Sensitive Elastin-Based Switches to Stabilize Globular Proteins
Elastin and elastin-based peptides display a temperature-dependent conformational transition from a less to a more ordered state upon increasing temperature , This inverse temperature behavior has been attributed to hydrophobic collapse and expulsion of water molecules associated with the non-polar side-chains of the polymer by both experimental  and simulation  studies. In addition, studies by Reiersen et al.  of various elastin monomers (VPGVG) suggest that short elastin-based peptides exhibit the same behavior as elastin. Also, an engineered protein A mini-domain containing an elastin turn exhibits reversible temperature-controlled IgG binding . Following along these lines, we now ask whether an elastin-based turn can serve as a temperature-sensitive switch when engineered into a globular protein such that its conformational behavior and stability can be controlled. We investigated this possibility using molecular dynamic simulations. These simulations suggest that it is possible to introduce an “inverse temperature transition” and/or stabilize a globular protein at higher temperature, by replacing a turn in the target protein with an elastin-like turn (VPGVG).
KeywordsDisulfide Bond Globular Protein Accessible Surface Area Solvent Accessible Surface Area Conformational Behavior