PCNA from Thermococcus gammatolerans: A protein involved in chromosomal DNA metabolism intrinsically resistant at high levels of ionizing radiation

Yerli Marín-Tovar, H. Serrano-Posada, A. Díaz-Vilchis, E. Rudiño-Piñera
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引用次数: 1

Abstract

Proliferating cell nuclear antigen (PCNA) is an essential protein for cell viability in archaea and eukarya, since it is involved in DNA replication and repair. In order to obtain insights regarding the characteristics that confer radioresistance, the structural study of the PCNA from Thermococcus gammatolerans (PCNATg) in a gradient of ionizing radiation by X‐ray crystallography was carried out, together with a bioinformatic analysis of homotrimeric PCNA structures, their sequences, and their molecular interactions. The results obtained from the datasets and the accumulated radiation dose for the last collection from three crystals revealed moderate and localized damage, since even with the loss of resolution, the electron density map corresponding to the last collection allowed to build the whole structure. Attempting to understand this behavior, multiple sequence alignments, and structural superpositions were performed, revealing that PCNA is a protein with a poorly conserved sequence, but with a highly conserved structure. The PCNATg presented the highest percentage of charged residues, mostly negatively charged, with a proportion of glutamate more than double aspartate, lack of cysteines and tryptophan, besides a high number of salt bridges. The structural study by X‐ray crystallography reveals that the PCNATg has the intrinsic ability to resist high levels of ionizing radiation, and the bioinformatic analysis suggests that molecular evolution selected a particular composition of amino acid residues, and their consequent network of synergistic interactions for extreme conditions, as a collateral effect, conferring radioresistance to a protein involved in the chromosomal DNA metabolism of a radioresistant microorganism.
来自伽马热球菌的PCNA:一种参与染色体DNA代谢的蛋白质,内在地抵抗高水平的电离辐射
增殖细胞核抗原(PCNA)是古细菌和真核生物中维持细胞活力所必需的蛋白,它参与DNA的复制和修复。为了获得有关赋予辐射抗性的特性的见解,利用X射线晶体学对来自伽马热球菌(PCNA)的PCNA在电离辐射梯度下的结构进行了研究,并对同源三聚体PCNA结构、序列和分子相互作用进行了生物信息学分析。从数据集和最后一次收集的三个晶体的累积辐射剂量中获得的结果显示出中度和局部损伤,因为即使在分辨率损失的情况下,与最后一次收集的电子密度图相对应的电子密度图也允许构建整个结构。为了理解这种行为,进行了多序列比对和结构叠加,揭示了PCNA是一种序列保守性差但结构高度保守的蛋白质。PCNATg的带电残基比例最高,大部分带负电,谷氨酸的比例超过天冬氨酸的两倍,缺乏半胱氨酸和色氨酸,此外还有大量的盐桥。X射线晶体学的结构研究表明,PCNATg具有抵抗高水平电离辐射的内在能力,生物信息学分析表明,分子进化选择了氨基酸残基的特定组成,以及它们在极端条件下的协同相互作用网络,作为附带效应,赋予抗辐射微生物染色体DNA代谢中涉及的蛋白质抗辐射能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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