在1.7 Å分辨率下,雪梨纤维蛋白与天然结合的s -腺苷- l-蛋氨酸复合物的结构。

IF 0.9 4区 生物学
Udesh de Silva, Zhaoli Zhou, Bernard A Brown
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引用次数: 5

摘要

纤原蛋白是C/D类小核核糖核蛋白(snRNPs)相关的关键甲基转移酶,参与核糖体前rRNA加工的初步步骤。这种分子存在于真核生物核仁的纤维区,参与rRNA中核糖2'-O原子的甲基化。人纤维蛋白含有一个n端GAR结构域,一个中心rna结合结构域,包括一个类似rnp -2的超家族一致序列和一个催化c端螺旋结构域。本文描述了与人纤维蛋白c端结构域同源的雪梨纤维蛋白。该蛋白与活性位点结合的s -腺苷- l-蛋氨酸(SAM)配体结晶。该配合物的分子结构通过x射线晶体学以1.7 Å的分辨率通过纤维蛋白结构同源物的分子替换来解决。该结构显示了SAM的原子细节及其活性位点相互作用;有许多保守残基直接与辅因子相互作用。值得注意的是,SAM的腺嘌呤环通过与保守残基Phe110的π-π相互作用以及与Asp134、Ala135和Gln157残基的静电相互作用而稳定。π-π相互作用似乎在稳定SAM与纤维蛋白的关联中起关键作用。此外,通过与同源结构的茴香纤维蛋白比较,发现了Phe110的不同取向和纤维蛋白α-螺旋6的变化,并提示其与SAM活性位点腺嘌呤环和C/D RNA的相互作用存在关键差异。这些差异可能在SAM配体定向催化、其他核糖核蛋白的组装以及与C/D RNA的相互作用中发挥关键作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Structure of Aeropyrum pernix fibrillarin in complex with natively bound S-adenosyl-L-methionine at 1.7 Å resolution.

Structure of Aeropyrum pernix fibrillarin in complex with natively bound S-adenosyl-L-methionine at 1.7 Å resolution.

Fibrillarin is the key methyltransferase associated with the C/D class of small nuclear ribonucleoproteins (snRNPs) and participates in the preliminary step of pre-ribosomal rRNA processing. This molecule is found in the fibrillar regions of the eukaryotic nucleolus and is involved in methylation of the 2'-O atom of ribose in rRNA. Human fibrillarin contains an N-terminal GAR domain, a central RNA-binding domain comprising an RNP-2-like superfamily consensus sequence and a catalytic C-terminal helical domain. Here, Aeropyrum pernix fibrillarin is described, which is homologous to the C-terminal domain of human fibrillarin. The protein was crystallized with an S-adenosyl-L-methionine (SAM) ligand bound in the active site. The molecular structure of this complex was solved using X-ray crystallography at a resolution of 1.7 Å using molecular replacement with fibrillarin structural homologs. The structure shows the atomic details of SAM and its active-site interactions; there are a number of conserved residues that interact directly with the cofactor. Notably, the adenine ring of SAM is stabilized by π-π interactions with the conserved residue Phe110 and by electrostatic interactions with the Asp134, Ala135 and Gln157 residues. The π-π interaction appears to play a critical role in stabilizing the association of SAM with fibrillarin. Furthermore, comparison of A. pernix fibrillarin with homologous structures revealed different orientations of Phe110 and changes in α-helix 6 of fibrillarin and suggests key differences in its interactions with the adenine ring of SAM in the active site and with the C/D RNA. These differences may play a key role in orienting the SAM ligand for catalysis as well as in the assembly of other ribonucleoproteins and in the interactions with C/D RNA.

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期刊介绍: Acta Crystallographica Section F is a rapid structural biology communications journal. Articles on any aspect of structural biology, including structures determined using high-throughput methods or from iterative studies such as those used in the pharmaceutical industry, are welcomed by the journal. The journal offers the option of open access, and all communications benefit from unlimited free use of colour illustrations and no page charges. Authors are encouraged to submit multimedia content for publication with their articles. Acta Cryst. F has a dedicated online tool called publBio that is designed to make the preparation and submission of articles easier for authors.
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