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首页 » PNAS报道 » PNAS:拟南芥中寡肽酶或可降解阿尔兹海默氏症患者大脑中的β-淀粉样蛋白

PNAS:拟南芥中寡肽酶或可降解阿尔兹海默氏症患者大脑中的β-淀粉样蛋白

来源:生物谷 2013-09-23 22:07

2013年9月24日 讯 /生物谷BIOON/ --近日,刊登在国际杂志Proceedings of the National Academy of Sciences上的一篇研究报告中,来自西澳大学的研究者通过研究揭开了阿尔兹海默氏症治疗的新策略,该研究为揭示机体细胞中的短肽降解提供了新的数据。

文章中,研究者在拟南芥中鉴别出了一种新型的寡肽酶(OligoPeptidase,OOP),而拟南芥又是很多分子生物学家研究的一种模式生物,研究者发现,OPP可以降解一些进入到线粒体和叶绿体中的小型肽类,蛋白质进入到细胞器中对于维持细胞功能非常重要,但是小型肽类必须被降解破坏,因为其对机体细胞具有毒性影响。

研究者Jim Whelan教授表示,在模式物种中肽类降解的途径的特点对于我们理解动物和植物疾病中蛋白酶所扮演的角色非常重要。

前序列蛋白酶(PreP),其首次是在植物中被定义的,研究者发现,其也可以降解阿尔兹海默氏症病人大脑中的β-淀粉样蛋白肽类。研究者认为,OOP和PreP可以“合作”来完成破坏患者大脑中有害肽类的积累以及逆转患者病情。

最后研究者表示研究人类机体OOP的变体非常有意思,通过研究就可以理解其降解β-淀粉样蛋白肽类的作用,其对于理解阿尔兹海默氏症患者的病情以及老化伴随病的发病机制非常重要,而且可以帮助研究者开发出新型疗法来治疗患者疾病。(生物谷Bioon.com)

Organellar oligopeptidase (OOP) provides a complementary pathway for targeting peptide degradation in mitochondria and chloroplasts

Beata Kmieca,1, Pedro F. Teixeiraa,1, Ronnie P.-A. Berntssona, Monika W. Murchab, Rui M. M. Brancac, Jordan D. Radomiljacb,d, Jakob Regberge, Linda M. Svenssona, Amin Bakalia, Ülo Langele, Janne Lehtiöc, James Whelanb,f, Pål Stenmarka, and Elzbieta Glasera,2

Both mitochondria and chloroplasts contain distinct proteolytic systems for precursor protein processing catalyzed by the mitochondrial and stromal processing peptidases and for the degradation of targeting peptides catalyzed by presequence protease. Here, we have identified and characterized a component of the organellar proteolytic systems in Arabidopsis thaliana, the organellar oligopeptidase, OOP (At5g65620). OOP belongs to the M3A family of peptide-degrading metalloproteases. Using two independent in vivo methods, we show that the protease is dually localized to mitochondria and chloroplasts. Furthermore, we localized the OPP homolog At5g10540 to the cytosol. Analysis of peptide degradation by OOP revealed substrate size restriction from 8 to 23 aa residues. Short mitochondrial targeting peptides (presequence of the ribosomal protein L29 and presequence of 1-aminocyclopropane-1-carboxylic acid deaminase 1) and N- and C-terminal fragments derived from the presequence of the ATPase beta subunit ranging in size from 11 to 20 aa could be degraded. MS analysis showed that OOP does not exhibit a strict cleavage pattern but shows a weak preference for hydrophobic residues (F/L) at the P1 position. The crystal structures of OOP, at 1.8–1.9 Å, exhibit an ellipsoidal shape consisting of two major domains enclosing the catalytic cavity of 3,000 Å3. The structural and biochemical data suggest that the protein undergoes conformational changes to allow peptide binding and proteolysis. Our results demonstrate the complementary role of OOP in targeting-peptide degradation in mitochondria and chloroplasts.

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