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消除RNA镁泡。立体化学来帮忙!

Deflating the RNA Mg bubble. Stereochemistry to the rescue!

作者信息

Auffinger Pascal, Ennifar Eric, D'Ascenzo Luigi

机构信息

IBMC - UPR9002 - CNRS;

IBMC - UPR9002 - CNRS.

出版信息

RNA. 2020 Dec 2;27(3):243-52. doi: 10.1261/rna.076067.120.

Abstract

Proper evaluation of the ionic structure of biomolecular systems through X ray and cryo-EM techniques remains challenging but is essential for advancing our understanding of the underlying structure/activity/solvent relationships. However, numerous studies overestimate the number of Mg2+ in deposited structures due to assignment errors finding their origin in improper consideration of stereochemical rules. Herein, to tackle such issues, we re-evaluate the PDBid 6QNR and 6SJ6 models of the ribosome ionic structure. We establish that stereochemical principles need to be carefully pondered when evaluating ion binding features, even when K+ anomalous signals are available as it is the case for the 6QNR PDB entry. For ribosomes, assignment errors can result in misleading conceptions of their solvent structure. For instance, present stereochemical analysis result in a significant decrease of the number of assigned Mg2+ in 6QNR, suggesting that K+ and not Mg2+ is the prevalent ion in the ribosome 1st solvation shell. We stress that the use of proper stereochemical guidelines in combination or not with other identification techniques, such as those pertaining to the detection of transition metals, of some anions and of K+ anomalous signals, is critical for deflating the current Mg2+ bubble witnessed in many ribosome and other RNA structures. We also stress that for the identification of lighter ions such as Mg2+, Na+, …, for which no anomalous signals can be detected, stereochemistry coupled with high resolution structures (<2.4 Å) remain the best currently available option.

摘要

通过X射线和冷冻电镜技术对生物分子系统的离子结构进行恰当评估仍然具有挑战性,但对于推进我们对潜在的结构/活性/溶剂关系的理解至关重要。然而,由于在确定离子时考虑立体化学规则不当而导致的赋值错误,众多研究高估了沉积结构中Mg2+的数量。在此,为解决此类问题,我们重新评估了核糖体离子结构的PDB编号6QNR和6SJ6模型。我们确定,在评估离子结合特征时需要仔细考虑立体化学原理,即使在有K+反常信号的情况下也是如此,就像6QNR PDB条目那样。对于核糖体而言,赋值错误可能导致对其溶剂结构产生误导性的概念。例如,目前的立体化学分析结果显示6QNR中指定的Mg2+数量显著减少,这表明核糖体第一溶剂化层中普遍存在的离子是K+而非Mg2+。我们强调,使用适当的立体化学指导原则,无论是否与其他识别技术(如与过渡金属、某些阴离子和K+反常信号检测相关的技术)相结合,对于消除目前在许多核糖体和其他RNA结构中出现的Mg2+泡沫至关重要。我们还强调,对于识别诸如Mg2+、Na+等无法检测到反常信号的较轻离子,立体化学与高分辨率结构(<2.4 Å)相结合仍然是目前最好的可用选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1492/7901845/91d9c7406e05/243f01.jpg

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