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从蛋白质组学角度确定结构生物学的目标:嗜γ热球菌的古菌蛋白TGAM_1934

Prioritizing targets for structural biology through the lens of proteomics: the archaeal protein TGAM_1934 from Thermococcus gammatolerans.

作者信息

Yang Yin-Shan, Fernandez Bernard, Lagorce Arnaud, Aloin Valérie, De Guillen Karine Montet, Boyer Jean-Baptiste, Dedieu Alain, Confalonieri Fabrice, Armengaud Jean, Roumestand Christian

机构信息

Centre de Biochimie Structurale, Universités de Montpellier, Montpellier, France.

出版信息

Proteomics. 2015 Jan;15(1):114-23. doi: 10.1002/pmic.201300535.

DOI:10.1002/pmic.201300535
PMID:25359407
Abstract

ORFans are hypothetical proteins lacking any significant sequence similarity with other proteins. Here, we highlighted by quantitative proteomics the TGAM_1934 ORFan from the hyperradioresistant Thermococcus gammatolerans archaeon as one of the most abundant hypothetical proteins. This protein has been selected as a priority target for structure determination on the basis of its abundance in three cellular conditions. Its solution structure has been determined using multidimensional heteronuclear NMR spectroscopy. TGAM_1934 displays an original fold, although sharing some similarities with the 3D structure of the bacterial ortholog of frataxin, CyaY, a protein conserved in bacteria and eukaryotes and involved in iron-sulfur cluster biogenesis. These results highlight the potential of structural proteomics in prioritizing ORFan targets for structure determination based on quantitative proteomics data. The proteomic data and structure coordinates have been deposited to the ProteomeXchange with identifier PXD000402 (http://proteomecentral.proteomexchange.org/dataset/PXD000402) and Protein Data Bank under the accession number 2mcf, respectively.

摘要

孤儿蛋白是指那些与其他蛋白质缺乏任何显著序列相似性的假设性蛋白质。在此,我们通过定量蛋白质组学强调了来自超耐辐射嗜热栖热放线菌古菌的TGAM_1934孤儿蛋白,它是最丰富的假设性蛋白质之一。基于其在三种细胞条件下的丰度,该蛋白已被选为结构测定的优先目标。其溶液结构已通过多维异核核磁共振光谱法确定。TGAM_1934呈现出一种独特的折叠方式,尽管与细菌中frataxin的直系同源蛋白CyaY的三维结构有一些相似之处,CyaY是一种在细菌和真核生物中保守且参与铁硫簇生物合成的蛋白质。这些结果突出了结构蛋白质组学在基于定量蛋白质组学数据为结构测定确定孤儿蛋白目标优先级方面的潜力。蛋白质组学数据和结构坐标已分别以标识符PXD000402(http://proteomecentral.proteomexchange.org/dataset/PXD000402)存入蛋白质组交换库和蛋白质数据库,登录号为2mcf。

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