Structural and functional conservation of Mycobacterium tuberculosis GroEL paralogs suggests that GroEL1 Is a chaperonin.

Structural and functional conservation of Mycobacterium tuberculosis GroEL paralogs suggests that GroEL1 Is a chaperonin.
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DOI:
10.1016/j.jmb.2010.11.021
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发表时间:
2011-01-21
影响因子:
5.6
通讯作者:
Tsai FT
Tsai FT
中科院分区:
生物学2区
文献类型:
--
作者:
Sielaff B;Lee KS;Tsai FT

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GroEL是一种I组伴侣蛋白,可促进蛋白质折叠并防止蛋白质在细菌胞浆中聚集。分枝杆菌在其基因组中编码两个或更多个GroEL副本是不寻常的。虽然GroEL2对于生存和可能作为一般管家伴侣的功能是必不可少的,但GroEL1是可有可无的,但其结构和功能尚不清楚。在这里,我们展示了结核分枝杆菌GroEL1的一个23 kDa片段的2.2?分辨率晶体结构,该片段由一个扩展的顶端结构域组成。我们GroEL1顶端结构域的X射线结构与大肠杆菌GroEL和结核分枝杆菌GroEL2的结构非常相似;因此,突出了细菌伴侣蛋白显著的结构保守性。值得注意的是,在我们的结构中,GroEL1的底物结合位点与一个对称相关的相邻GroEL1分子的N端区域相互作用。后者与已知的GroEL顶端结构域在底物结合中的功能是一致的,并得到了使用肽阵列技术获得的结果的支持。综上所述,我们表明结核分枝杆菌GroEL Paralog的顶端结构域在三维结构中是保守的,表明GroEL1和GroEL2一样,是一种伴侣蛋白。
GroEL is a group I chaperonin that facilitates protein folding and prevents protein aggregation in the bacterial cytosol. Mycobacteria are unusual in encoding two or more copies of GroEL in their genome. While GroEL2 is essential for viability and likely functions as the general housekeeping chaperonin, GroEL1 is dispensable but its structure and function remain unclear. Here we present the 2.2 Å resolution crystal structure of a 23 kDa fragment of Mycobacterium tuberculosis GroEL1 consisting of an extended apical domain. Our X-ray structure of the GroEL1 apical domain closely resembles those of Escherichia coli GroEL and M. tuberculosis GroEL2; thus, highlighting the remarkable structural conservation of bacterial chaperonins. Notably, in our structure, the proposed substrate-binding site of GroEL1 interacts with the N-terminal region of a symmetry related, neighboring GroEL1 molecule. The latter is consistent with the known GroEL apical domain function in substrate binding, and is supported by results obtained from using peptide array technology. Taken together, we show that the apical domains of M. tuberculosis GroEL paralogs are conserved in three-dimensional structure, suggesting that GroEL1, like GroEL2, is a chaperonin.
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