Nuclease activity of Plasmodium falciparum Alba family protein PfAlba3.

Plasmodium falciparum Alba domain-containing protein Alba3 (PfAlba3) is ubiquitously expressed in intra-erythrocytic stages of Plasmodium falciparum, but the function of this protein is not yet established. Here, we report an apurinic/apyrimidinic site-driven intrinsic nuclease activity of PfAlba3 assisted by divalent metal ions. Surface plasmon resonance and atomic force microscopy confirm sequence non-specific DNA binding by PfAlba3. Upon binding, PfAlba3 cleaves double-stranded DNA (dsDNA) hydrolytically. Mutational studies coupled with mass spectrometric analysis indicate that K23 is the essential residue in modulating the binding to DNA through acetylation-deacetylation. We further demonstrate that PfSir2a interacts and deacetylates K23-acetylated PfAlba3 in favoring DNA binding. Hence, K23 serves as a putative molecular switch regulating the nuclease activity of PfAlba3. Thus, the nuclease activity of PfAlba3, along with its apurinic/apyrimidinic (AP) endonuclease feature identified in this study, indicates a role of PfAlba3 in DNA-damage response that may have a far-reaching consequence in Plasmodium pathogenicity. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Chinmoy Banerjee, Shiladitya Nag, Manish Goyal, Debanjan Saha, Asim Azhar Siddiqui, Somnath Mazumder, Subhashis Debsharma, Saikat Pramanik, Uday Bandyopadhyay. Nuclease activity of Plasmodium falciparum Alba family protein PfAlba3. Cell reports. 2023 Apr 25;42(4):112292

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PMID: 36947546

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