Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
mBio. 2021 Jun 29;12(3):e0076021. doi: 10.1128/mBio.00760-21.
During its complex life cycle, the malaria parasite survives dramatic environmental stresses, including large temperature shifts. Protein prenylation is required during asexual replication of Plasmodium falciparum, and the canonical heat shock protein 40 protein (HSP40; PF3D7_1437900) is posttranslationally modified with a 15-carbon farnesyl isoprenyl group. In other organisms, farnesylation of Hsp40 orthologs controls their localization and function in resisting environmental stress. In this work, we find that plastidial isopentenyl pyrophosphate (IPP) synthesis and protein farnesylation are required for malaria parasite survival after cold and heat shock. Furthermore, loss of HSP40 farnesylation alters its membrane attachment and interaction with proteins in essential pathways in the parasite. Together, this work reveals that farnesylation is essential for parasite survival during temperature stress. Farnesylation of HSP40 may promote thermotolerance by guiding distinct chaperone-client protein interactions.
在其复杂的生命周期中，疟原虫能够在包括大幅温度变化在内的各种恶劣环境中存活下来。疟原虫裂殖体（Plasmodium falciparum）的无性繁殖需要蛋白质的异戊烯基化，而典型的热休克蛋白 40 蛋白（HSP40；PF3D7_1437900）则通过 15 个碳的法呢基异戊烯基基团进行翻译后修饰。在其他生物体中，Hsp40 同源物的法尼基化控制着它们在抵抗环境压力时的定位和功能。在这项工作中，我们发现质体异戊烯焦磷酸（IPP）合成和蛋白质法尼基化对于疟原虫在冷、热休克后的存活是必需的。此外，HSP40 法尼基化的丧失改变了其与寄生虫中重要途径中的蛋白质的膜附着和相互作用。总之，这项工作揭示了法尼基化对于寄生虫在温度应激下存活是必不可少的。HSP40 的法尼基化可能通过指导不同伴侣蛋白-客户蛋白相互作用来促进耐热性。
