Departamento de Ciencia y Tecnología, CONICET, Universidad Nacional de Quilmes, Roque Sáenz Peña 352, B1876BXD, Bernal, Provincia de Buenos Aires, Argentina.
Departamento de Ciencia y Tecnología, CONICET, Universidad Nacional de Quilmes, Roque Sáenz Peña 352, B1876BXD, Bernal, Provincia de Buenos Aires, Argentina; Department of Biomedical Sciences, University of Padua, Padua, Italy.
J Mol Biol. 2019 Mar 15;431(6):1298-1307. doi: 10.1016/j.jmb.2019.01.031. Epub 2019 Feb 5.
The conformations accessible to proteins are determined by the inter-residue interactions between amino acid residues. During evolution, structural constraints that are required for protein function providing biologically relevant information can exist. Here, we studied the proportion of sites evolving under structural constraints in two very different types of ensembles, those coming from ordered and disordered proteins. Using a structurally constrained model of protein evolution, we found that both types of ensembles show comparable, near 40%, number of positions evolving under structural constraints. Among these sites, ~68% are in disordered regions and ~57% of them show long-range inter-residue contacts. Also, we found that disordered ensembles are redundant in reference to their structurally constrained evolutionary information and could be described on average with ~11 conformers. Despite the different complexity of the studied ensembles and proteins, the similar constraints reveal a comparable level of selective pressure to maintain their biological functions. These results highlight the importance of the evolutionary information to recover meaningful biological information to further characterize conformational ensembles.
蛋白质的构象由氨基酸残基之间的相互作用决定。在进化过程中，可能存在为蛋白质功能提供生物学相关信息的结构约束。在这里，我们研究了来自有序和无序蛋白质的两种截然不同的集合中受结构约束的位置的比例。使用蛋白质进化的结构约束模型，我们发现这两种集合都显示出可比较的、接近 40%的受结构约束的位置数量。在这些位置中，68%位于无序区域，其中57%显示长程残基间相互作用。此外，我们发现无序集合在其结构约束进化信息方面是冗余的，并且可以平均用~11 种构象来描述。尽管研究的集合和蛋白质的复杂性不同，但相似的约束揭示了维持其生物功能的类似选择压力。这些结果强调了进化信息对于恢复有意义的生物学信息以进一步描述构象集合的重要性。
