García-Arévalo C, Quintanilla-Sierra L, Santos M, Ferrero S, Acosta S, Rodríguez-Cabello J C
GIR Bioforge, Universidad de Valladolid, CIBER-BBN, Paseo de Belén 9, 47011, Valladolid, Spain.
GIR MIOMeT, IU CINQUIMA/Química Inorgánica, Facultad de Ciencias, Universidad de Valladolid, 47011, Valladolid, Spain.
Mater Today Bio. 2022 Aug 18;16:100400. doi: 10.1016/j.mtbio.2022.100400. eCollection 2022 Dec.
Understanding the interplay between order and disorder in intrinsically disorder proteins (IDPs), and its impact on the properties and features of materials manufactured from them, is a major challenge in the design of protein-based synthetic polymers intended for advanced functions. In this paper an elastin-like diblock co-recombinamer amphiphile (Phe-ELR) based on a hydrophobic block containing five phenylalanine (Phe) residues proximal to the carboxyl function of a glutamic acid (Glu) residue upon folding, and with Glu as the guest residue in the hydrophilic part, was engineered and its assembly behaviour compared with another amphiphilic ELR used as control. Phe-ELR was tailored in order to clarify the impact of the presence of aromatic residues in the amino acid sequence, which even in early studies by Urry's group already demonstrated a certain out-of-trend behaviour compared with other apolar amino acids, especially non-aromatic ones, on ELR behaviour. The combination of several experimental techniques indicates strong molecular interactions associated with the Phe residue, thus resulting in limited reversible character of the temperature-induced transitions during sequential thermal cycles, a lower than expected transition enthalpy, and clear differences in its supramolecular assembly with respect to the control ELR. A distinctive pre-aggregated state for the Phe-ELR under any condition of pH and temperature is found. Eventually, this state gives rise to Phe-core micelles or a solid jelly-like material, depending on the concentration, pH and presence of salts. In conclusion, it appears that the presence of aromatic residues and their ability to promote strong inter- and intramolecular interactions at any temperature and pH causes a complete modification of the order-disorder interplay present in other, non-aromatic ELRs. These molecular events have a profound impact on the physical properties of the resulting polymer when compared with other ELRs. This work helps to shed light on the limits that govern intrinsic disorder in ELRs beyond its inverse temperature transition.
理解内在无序蛋白（IDP）中有序与无序之间的相互作用，以及其对由它们制造的材料的性质和特征的影响，是设计用于高级功能的基于蛋白质的合成聚合物的一项重大挑战。在本文中，设计了一种基于弹性蛋白样二嵌段共重组体两亲物（Phe-ELR），其疏水嵌段在折叠时靠近谷氨酸（Glu）残基的羧基功能处含有五个苯丙氨酸（Phe）残基，且在亲水部分以Glu作为客体残基，并将其组装行为与用作对照的另一种两亲性弹性蛋白样重组体（ELR）进行了比较。对Phe-ELR进行了定制，以阐明氨基酸序列中芳香族残基的存在所产生的影响，即使在厄里小组早期的研究中就已表明，与其他非极性氨基酸，尤其是非芳香族氨基酸相比，芳香族残基对弹性蛋白样重组体行为具有一定的异常行为。多种实验技术的结合表明，与Phe残基存在强烈的分子相互作用，从而导致在连续热循环过程中温度诱导转变的可逆性有限、转变焓低于预期，以及其超分子组装相对于对照ELR存在明显差异。发现在任何pH和温度条件下，Phe-ELR都具有独特的预聚集状态。最终，根据浓度、pH和盐的存在情况，这种状态会产生以Phe为核心的胶束或固体果冻状材料。总之，似乎芳香族残基的存在及其在任何温度和pH下促进强分子间和分子内相互作用的能力，导致了其他非芳香族ELR中存在的有序-无序相互作用的完全改变。与其他ELR相比，这些分子事件对所得聚合物的物理性质产生了深远影响。这项工作有助于揭示除了其逆温度转变之外，控制ELR内在无序的限制因素。
