Functional Interplay between P5 and PDI/ERp72 to Drive Protein Folding.
Functional Interplay between P5 and PDI/ERp72 to Drive Protein Folding.
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DOI：
10.3390/biology10111112
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发表时间：
2021-10-28
期刊：
影响因子：
4.2
通讯作者：
Okumura M
中科院分区：
文献类型：
--
作者：
Matsusaki M;Okada R;Tanikawa Y;Kanemura S;Ito D;Lin Y;Watabe M;Yamaguchi H;Saio T;Lee YH;Inaba K;Okumura M
蛋白质独特的三维结构决定了其生理功能。几乎所有的生物界都共享保守的二硫化物催化剂和分子伴侣网络，这些网络有助于正确的蛋白质折叠和防止聚集。这些网络的破坏涉及发病机制，包括神经退行性疾病。在哺乳动物内质网（ER）中，蛋白质二硫键异构酶家族（PDI）的20多个成员被认为在客户端折叠途径中合作，但仍然不清楚PDI之间通过非共价相互作用形成的复合物是否参与调节其酶和伴侣功能。在此，我们报告了新的功能杂合物之间的PDIs，促进氧化折叠和抑制聚集沿着客户端折叠。这些发现提供了深入了解二硫化物催化剂和伴侣网络的生理意义，并为理解与网络破坏相关的发病机制提供了线索。P5是一种蛋白质二硫键异构酶家族蛋白（PDIs），参与内质网（ER）蛋白质质量控制，辅助氧化折叠，抑制蛋白质聚集，并调节未折叠蛋白质反应。据报道，P5在培养的细胞中通过分子间二硫键与其他PDI相互作用，但仍不清楚P5和其他PDI之间的复合物形成是否参与调节酶和伴侣蛋白功能。在此，我们建立了far-western blot方法来检测P5与其他PDI之间的非共价相互作用，并发现PDI和ERp 72是P5的伴侣蛋白。P5介导的氧化折叠的酶活性被PDI上调，而P5的伴侣活性被ERp 72刺激。这些发现揭示了PDI之间的复合物形成协同加速蛋白质折叠并防止聚集的机制。这些知识对理解错误折叠相关的病理学有影响。
The physiological functions of proteins are destined by their unique three-dimensional structures. Almost all biological kingdoms share conserved disulfide-catalysts and chaperone networks that assist in correct protein folding and prevent aggregation. Disruption of these networks is implicated in pathogenesis, including neurodegenerative disease. In the mammalian endoplasmic reticulum (ER), more than 20 members of the protein disulfide isomerase family (PDIs) are believed to cooperate in the client folding pathway, but it remains unclear whether complex formation among PDIs via non-covalent interaction is involved in regulating their enzymatic and chaperone functions. Herein, we report novel functional hetero complexes between PDIs that promote oxidative folding and inhibit aggregation along client folding. The findings provide insight into the physiological significance of disulfide-catalyst and chaperone networks and clues for understanding pathogenesis associated with disruption of the networks. P5 is one of protein disulfide isomerase family proteins (PDIs) involved in endoplasmic reticulum (ER) protein quality control that assists oxidative folding, inhibits protein aggregation, and regulates the unfolded protein response. P5 reportedly interacts with other PDIs via intermolecular disulfide bonds in cultured cells, but it remains unclear whether complex formation between P5 and other PDIs is involved in regulating enzymatic and chaperone functions. Herein, we established the far-western blot method to detect non-covalent interactions between P5 and other PDIs and found that PDI and ERp72 are partner proteins of P5. The enzymatic activity of P5-mediated oxidative folding is up-regulated by PDI, while the chaperone activity of P5 is stimulated by ERp72. These findings shed light on the mechanism by which the complex formations among PDIs drive to synergistically accelerate protein folding and prevents aggregation. This knowledge has implications for understanding misfolding-related pathology.
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影响因子：
4
作者：
Eletto, Davide;Chevet, Eric;Appenzeller-Herzog, Christian
通讯作者：
Appenzeller-Herzog, Christian
影响因子：
2.7
作者：
Kikuchi, M;Doi, E;Tsujimoto, Y
通讯作者：
Tsujimoto, Y
影响因子：
5.6
作者：
Kanemura S;Matsusaki M;Inaba K;Okumura M
通讯作者：
Okumura M
DOI：
10.1083/jcb.201303027
发表时间：
2013-09-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Araki K;Iemura S;Kamiya Y;Ron D;Kato K;Natsume T;Nagata K
通讯作者：
Nagata K
影响因子：
8
作者：
Huang, GC;Li, ZY;Fischer, G
通讯作者：
Fischer, G