Plasmodium falciparum Alba6 exhibits DNase activity and participates in stress response

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

doi:10.1016/j.isci.2024.109467

Plasmodium falciparum Alba6 exhibits DNase activity and participates in stress response

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

Authors

Affiliations

¹ Division of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.
² Department of Molecular & Cell Biology, School of Dental Medicine, Boston University Medical Campus, Boston, MA, USA.
³ Department of Zoology, Raja Peary Mohan College, 1 Acharya Dhruba Pal Road, Uttarpara, West Bengal 712258, India.
⁴ Amity Institute of Biotechnology, Amity University, Kolkata, Plot No: 36, 37 & 38, Major Arterial Road, Action Area II, Kadampukur Village, Newtown, Kolkata, West Bengal 700135, India.
⁵ Division of Molecular Medicine, Bose Institute, Unified Academic Campus, EN 80, Sector V, Bidhan Nagar, Kolkata, West Bengal 700091, India.

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 Plasmodium falciparum, an etiological agent responsible for human malignant malaria. We identified that tyrosine28 plays a critical role in the Mg²⁺ 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.

Keywords: Biochemistry; Drugs; Microbiology parasite; Structural biology.