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阿尔巴6具有脱氧核糖核酸酶活性并参与应激反应。

Alba6 exhibits DNase activity and participates in stress response.

作者信息

Nag Shiladitya, Banerjee Chinmoy, Goyal Manish, Siddiqui Asim Azhar, Saha Debanjan, Mazumder Somnath, Debsharma Subhashis, Pramanik Saikat, Saha Shubhra Jyoti, De Rudranil, Bandyopadhyay Uday

机构信息

Division of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.

Department of Molecular & Cell Biology, School of Dental Medicine, Boston University Medical Campus, Boston, MA, USA.

出版信息

iScience. 2024 Mar 8;27(4):109467. doi: 10.1016/j.isci.2024.109467. eCollection 2024 Apr 19.

DOI:10.1016/j.isci.2024.109467
PMID:38558939
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10981135/
Abstract

Alba domain proteins, owing to their functional plasticity, play a significant role in organisms. Here, we report an intrinsic DNase activity of PfAlba6 from , an etiological agent responsible for human malignant malaria. We identified that tyrosine28 plays a critical role in the Mg driven 5'-3' DNase activity of PfAlba6. PfAlba6 cleaves both dsDNA as well as ssDNA. We also characterized PfAlba6-DNA interaction and observed concentration-dependent oligomerization in the presence of DNA, which is evident from size exclusion chromatography and single molecule AFM-imaging. PfAlba6 mRNA expression level is up-regulated several folds following heat stress and treatment with artemisinin, indicating a possible role in stress response. PfAlba6 has no human orthologs and is expressed in all intra-erythrocytic stages; thus, this protein can potentially be a new anti-malarial drug target.

摘要

阿尔巴结构域蛋白因其功能可塑性，在生物体中发挥着重要作用。在此，我们报道了来自恶性疟原虫（一种导致人类恶性疟疾的病原体）的PfAlba6的内在脱氧核糖核酸酶活性。我们确定酪氨酸28在PfAlba6的镁离子驱动的5'-3'脱氧核糖核酸酶活性中起关键作用。PfAlba6可切割双链脱氧核糖核酸以及单链脱氧核糖核酸。我们还对PfAlba6与脱氧核糖核酸的相互作用进行了表征，并观察到在存在脱氧核糖核酸的情况下其浓度依赖性寡聚化，这从尺寸排阻色谱法和单分子原子力显微镜成像中可以明显看出。热应激和青蒿素处理后，PfAlba6信使核糖核酸表达水平上调了数倍，表明其在应激反应中可能发挥作用。PfAlba6没有人类直系同源物，且在所有红细胞内阶段均有表达；因此，这种蛋白质有可能成为一种新的抗疟药物靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/7ba7bb9fd740/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/aa5137f0ee06/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/6cca11bc14ca/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/254f5ddee62a/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/4b38f365004e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/a22133dd6770/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/5748c027d88b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/91a0e89f21c9/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/038a2fc9fbdb/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/e0559625feaf/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/7ba7bb9fd740/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/aa5137f0ee06/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/6cca11bc14ca/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/254f5ddee62a/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/4b38f365004e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/a22133dd6770/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/5748c027d88b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/91a0e89f21c9/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/038a2fc9fbdb/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/e0559625feaf/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b6/10981135/7ba7bb9fd740/gr9.jpg

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