Nuclease activity of Plasmodium falciparum Alba family protein PfAlba3
Summary: 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...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723003030 |
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| author | Chinmoy Banerjee Shiladitya Nag Manish Goyal Debanjan Saha Asim Azhar Siddiqui Somnath Mazumder Subhashis Debsharma Saikat Pramanik Uday Bandyopadhyay |
| author_facet | Chinmoy Banerjee Shiladitya Nag Manish Goyal Debanjan Saha Asim Azhar Siddiqui Somnath Mazumder Subhashis Debsharma Saikat Pramanik Uday Bandyopadhyay |
| author_sort | Chinmoy Banerjee |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-09T22:15:02Z |
| format | Article |
| id | doaj.art-64aa472cca78475cab597bedad88d9c8 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-09T22:15:02Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-64aa472cca78475cab597bedad88d9c82023-03-23T04:35:30ZengElsevierCell Reports2211-12472023-04-01424112292Nuclease activity of Plasmodium falciparum Alba family protein PfAlba3Chinmoy Banerjee0Shiladitya Nag1Manish Goyal2Debanjan Saha3Asim Azhar Siddiqui4Somnath Mazumder5Subhashis Debsharma6Saikat Pramanik7Uday Bandyopadhyay8Division of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal 700032, IndiaDivision of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal 700032, IndiaDivision of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal 700032, IndiaDivision of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal 700032, IndiaDivision of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal 700032, IndiaDivision of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal 700032, IndiaDivision of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal 700032, IndiaDivision of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal 700032, IndiaDivision of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal 700032, India; Division of Molecular Medicine, Bose Institute, EN 80, Sector V, Bidhan Nagar Kolkata, 700091, West Bengal, India; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723003030CP: Microbiology |
| spellingShingle | 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 CP: Microbiology |
| title | Nuclease activity of Plasmodium falciparum Alba family protein PfAlba3 |
| title_full | Nuclease activity of Plasmodium falciparum Alba family protein PfAlba3 |
| title_fullStr | Nuclease activity of Plasmodium falciparum Alba family protein PfAlba3 |
| title_full_unstemmed | Nuclease activity of Plasmodium falciparum Alba family protein PfAlba3 |
| title_short | Nuclease activity of Plasmodium falciparum Alba family protein PfAlba3 |
| title_sort | nuclease activity of plasmodium falciparum alba family protein pfalba3 |
| topic | CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723003030 |
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