近日，美国纽约州立大学布法罗分校的Priya R. Banerjee及其研究小组与圣犹达儿童研究医院的Tanja Mittag等人合作并取得一项新进展。经过不懈努力，他们发现序列特异性相互作用决定了蛋白质冷凝物的粘弹性和老化动力学。相关研究成果已于2024年7月2日在国际知名学术期刊《自然—物理学》上发表。
该研究团队研究了由蛋白质hnRNP A1的朊病毒样低复杂性结构域，及其设计变体形成的冷凝物的序列编码和年龄依赖的粘弹性的决定因素。研究人员发现冷凝物的主要粘性形式是亚稳态麦克斯韦流体。劳斯-齐姆模型解释了冷凝物中蛋白质的网状组织，再现了测量的粘弹性模量。研究人员表明芳香粘合子间相互作用的强度决定了，弹性和粘性模量的序列特异性振幅以及弹性性质占主导地位的时间尺度。这些冷凝物在序列特定的时间尺度上经历物理老化。这是由间隔残基的突变所驱动的，这种突变削弱了主要粘性相的亚稳态。
冷凝物的老化伴随着无序到有序的转变，导致非纤维、富含β片、半结晶且具弹性的开尔文-福格特固体结构的形成。这项研究结果表明，序列语法，指的是在朊病毒样低复杂性结构域中粘合子与间隔子的氨基酸身份，已经进化到可以控制冷凝物中主要粘性流体相的亚稳态。在功能相关的时间尺度上，这种选择可能会导致从亚稳流体到全局稳定固体的转化障碍无法克服。
据悉，生物分子凝聚物是粘弹性材料。
附：英文原文
Title: Sequence-specific interactions determine viscoelasticity and ageing dynamics of protein condensates
Author: Alshareedah, Ibraheem, Borcherds, Wade M., Cohen, Samuel R., Singh, Anurag, Posey, Ammon E., Farag, Mina, Bremer, Anne, Strout, Gregory W., Tomares, Dylan T., Pappu, Rohit V., Mittag, Tanja, Banerjee, Priya R.
Issue&Volume: 2024-07-02
Abstract: Biomolecular condensates are viscoelastic materials. Here we investigate the determinants of the sequence-encoded and age-dependent viscoelasticity of condensates formed by the prion-like low-complexity domain of the protein hnRNP A1 and its designed variants. We find that the dominantly viscous forms of the condensates are metastable Maxwell fluids. A Rouse–Zimm model that accounts for the network-like organization of proteins within condensates reproduces the measured viscoelastic moduli. We show that the strengths of aromatic inter-sticker interactions determine sequence-specific amplitudes of elastic and viscous moduli and the timescales over which elastic properties dominate. These condensates undergo physical ageing on sequence-specific timescales. This is driven by mutations to spacer residues that weaken the metastability of dominantly viscous phases. The ageing of condensates is accompanied by disorder-to-order transitions, leading to the formation of non-fibrillar, β-sheet-containing, semi-crystalline, elastic, Kelvin–Voigt solids. Our results suggest that sequence grammars, which refer to amino acid identities of stickers versus spacers in prion-like low-complexity domains, have evolved to afford control over metastabilities of dominantly viscous fluid phases of condensates. This selection is likely to render barriers for conversion from metastable fluids to globally stable solids insurmountable on functionally relevant timescales.
DOI: 10.1038/s41567-024-02558-1
Source: https://www.nature.com/articles/s41567-024-02558-1