Characterization of PUD-1 and PUD-2, two proteins up-regulated in a long-lived daf-2 mutant.

Characterization of PUD-1 and PUD-2, two proteins up-regulated in a long-lived daf-2 mutant.
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DOI:
10.1371/journal.pone.0067158
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Dong MQ
Dong MQ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ding YH;Du YG;Luo S;Li YX;Li TM;Yoshina S;Wang X;Klage K;Mitani S;Ye K;Dong MQ

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C.在daf-2(功能丧失)(PUD)中上调的两种蛋白质--秀丽线虫PUD-1和PUD-2是同源的17-kD蛋白质,在胰岛素信号传导减少的长寿daf-2突变动物中具有大量增加。在这项研究中,我们发现PUD-1和PUD-2在肠和皮下组织中大量表达,并形成异二聚体。我们已经将它们的晶体结构解析到了1.9 μ m的分辨率,并发现这两种蛋白质在V形二聚体中采用了相似的β-夹心折叠。相反,它们的同源物PUD-3、PUD-4、PUDL-1和PUDL-2都是单体蛋白,在C.优雅因此,PUD-1/PUD-2异源二聚体可能具有不同于其家族成员的功能。pud-1和pud-2的过表达或缺失均不影响WT或daf-2突变动物的寿命,这表明它们在daf-2蠕虫中的诱导并不有助于长寿。奇怪的是,pud-1和pud-2的缺失与针对淀粉样β肽(1-42)诱导的麻痹的保护作用相关,这进一步增强了daf-2(RNAi)对Aβ的保护作用。
C. elegans PUD-1 and PUD-2, two proteins up-regulated in daf-2(loss-of-function) (PUD), are homologous 17-kD proteins with a large abundance increase in long-lived daf-2 mutant animals of reduced insulin signaling. In this study, we show that both PUD-1 and PUD-2 are abundantly expressed in the intestine and hypodermis, and form a heterodimer. We have solved their crystal structure to 1.9-Å resolution and found that both proteins adopt similar β-sandwich folds in the V-shaped dimer. In contrast, their homologs PUD-3, PUD-4, PUDL-1 and PUDL-2 are all monomeric proteins with distinct expression patterns in C. elegans. Thus, the PUD-1/PUD-2 heterodimer probably has a function distinct from their family members. Neither overexpression nor deletion of pud-1 and pud-2 affected the lifespan of WT or daf-2 mutant animals, suggesting that their induction in daf-2 worms does not contribute to longevity. Curiously, deletion of pud-1 and pud-2 was associated with a protective effect against paralysis induced by the amyloid β-peptide (1-42), which further enhanced the protection conferred by daf-2(RNAi) against Aβ.
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