2013年9月24日 訊 /生物谷BIOON/ --近日，刊登在國際雜誌Proceedings of the National Academy of Sciences上的一篇研究報告中，來自西澳大學的研究者通過研究揭開了阿爾茲海默氏症治療的新策略，該研究為揭示機體細胞中的短肽降解提供了新的數據。
文章中，研究者在擬南芥中鑑別出了一種新型的寡肽酶(OligoPeptidase，OOP)，而擬南芥又是很多分子生物學家研究的一種模式生物，研究者發現，OPP可以降解一些進入到線粒體和葉綠體中的小型肽類，蛋白質進入到細胞器中對於維持細胞功能非常重要，但是小型肽類必須被降解破壞，因為其對機體細胞具有毒性影響。
研究者Jim Whelan教授表示，在模式物種中肽類降解的途徑的特點對於我們理解動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義的，研究者發現，其也可以降解阿爾茲海默氏症病人大腦中的β-澱粉樣蛋白肽類。研究者認為，OOP和PreP可以「合作」來完成破壞患者大腦中有害肽類的積累以及逆轉患者病情。
最後研究者表示研究人類機體OOP的變體非常有意思，通過研究就可以理解其降解β-澱粉樣蛋白肽類的作用，其對於理解阿爾茲海默氏症患者的病情以及老化伴隨病的發病機制非常重要，而且可以幫助研究者開發出新型療法來治療患者疾病。（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.