Department of Biomedical Engineering, Campus Box 90281 and Center for Biologically Inspired Materials and Material Systems, Duke University, Durham, North Carolina 27708, United States.
Biomacromolecules. 2013 May 13;14(5):1514-9. doi: 10.1021/bm400167h. Epub 2013 Apr 8.
Elastin-like polypeptides (ELPs) are thermally sensitive peptide polymers that undergo thermally triggered phase separation and this behavior is imparted to soluble proteins when they are fused to an ELP. The transition temperature of the ELP fusion protein is observed to be different than that of a free ELP, indicating that the surface properties of the fused protein modulate the thermal behavior of ELPs. Understanding this effect is important for the rational design of applications that exploit the phase transition behavior of ELP fusion proteins. We had previously developed a biophysical model that explained the effect of hydrophobic proteins on depressing the transition temperature of ELP fusion proteins relative to free ELP. Here, we extend the model to elucidate the effect of hydrophilic proteins on the thermal behavior of ELP fusion proteins. A linear correlation was found between overall residue composition of accessible protein surface weighted by a characteristic transition temperature for each residue and the difference in transition temperatures between the ELP protein fusion and the corresponding free ELP. In breaking down the contribution of residues to polar, nonpolar, and charged, the model revealed that charged residues are the most important parameter in altering the transition temperature of an ELP fusion relative to the free ELP.
弹性蛋白样多肽 (ELPs) 是热敏感的肽聚合物，它们经历热触发的相分离，当它们与 ELP 融合时，这种行为赋予可溶性蛋白质。ELP 融合蛋白的转变温度与游离 ELP 的转变温度不同，这表明融合蛋白的表面性质调节了 ELPs 的热行为。了解这种效应对于合理设计利用 ELP 融合蛋白的相变行为的应用非常重要。我们之前开发了一种生物物理模型，该模型解释了疏水蛋白对降低 ELP 融合蛋白相对于游离 ELP 的转变温度的影响。在这里，我们扩展了该模型以阐明亲水蛋白对 ELP 融合蛋白热行为的影响。发现可及蛋白质表面的整体残基组成与每个残基的特征转变温度的乘积与 ELP 蛋白融合与相应游离 ELP 之间转变温度的差异之间存在线性相关性。在对残基的极性、非极性和带电贡献进行分解时，该模型表明，与游离 ELP 相比，带电残基是改变 ELP 融合转变温度的最重要参数。
