Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexes
Abstract Ubiquitination is the key eukaryotic post-translational modification that governs protein degradation, localisation, and activity which is mediated by a concerted enzyme cascade. The largest superfamily of these enzymes include the Cullin-RING-Ligase (CRL) complexes. Plasmodium falciparum,...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-05342-0 |
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| author | Danushka Marapana Simon A. Cobbold Michal Pasternak Gerald J. Shami Stuart A. Ralph Sash Lopaticki Jumana Yousef Vineet Vaibhav Laura F. Dagley David Komander Alan F. Cowman |
| author_facet | Danushka Marapana Simon A. Cobbold Michal Pasternak Gerald J. Shami Stuart A. Ralph Sash Lopaticki Jumana Yousef Vineet Vaibhav Laura F. Dagley David Komander Alan F. Cowman |
| author_sort | Danushka Marapana |
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| description | Abstract Ubiquitination is the key eukaryotic post-translational modification that governs protein degradation, localisation, and activity which is mediated by a concerted enzyme cascade. The largest superfamily of these enzymes include the Cullin-RING-Ligase (CRL) complexes. Plasmodium falciparum, the causative agent of the most severe form of malaria in humans, encodes the critical proteins required for ubiquitination, but we do not yet understand the function of this pathway. Here the P. falciparum CRL complexes were characterised to reveal an essential but minimal repertoire controlled by two Cullin scaffolds. A PfCullin1-linked CRL complex, recruiting a single substrate receptor, was identified as being required for parasite inner-membrane biogenesis and DNA replication. A second CRL complex functioning through a PfCullin4 scaffold was identified that utilised a previously unidentified adaptor protein and receptors to support DNA replication. These results show that the P. falciparum CRL complexes are essential in both nuclear maintenance and membrane integrity. |
| format | Article |
| id | doaj-art-8e216aa18a704d409befa15a9db612df |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-8e216aa18a704d409befa15a9db612df2025-08-20T04:01:25ZengNature PortfolioScientific Reports2045-23222025-07-0115112010.1038/s41598-025-05342-0Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexesDanushka Marapana0Simon A. Cobbold1Michal Pasternak2Gerald J. Shami3Stuart A. Ralph4Sash Lopaticki5Jumana Yousef6Vineet Vaibhav7Laura F. Dagley8David Komander9Alan F. Cowman10The Walter and Eliza Hall Institute of Medical ResearchThe Walter and Eliza Hall Institute of Medical ResearchThe Walter and Eliza Hall Institute of Medical ResearchDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of MelbourneDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of MelbourneThe Walter and Eliza Hall Institute of Medical ResearchThe Walter and Eliza Hall Institute of Medical ResearchThe Walter and Eliza Hall Institute of Medical ResearchThe Walter and Eliza Hall Institute of Medical ResearchThe Walter and Eliza Hall Institute of Medical ResearchThe Walter and Eliza Hall Institute of Medical ResearchAbstract Ubiquitination is the key eukaryotic post-translational modification that governs protein degradation, localisation, and activity which is mediated by a concerted enzyme cascade. The largest superfamily of these enzymes include the Cullin-RING-Ligase (CRL) complexes. Plasmodium falciparum, the causative agent of the most severe form of malaria in humans, encodes the critical proteins required for ubiquitination, but we do not yet understand the function of this pathway. Here the P. falciparum CRL complexes were characterised to reveal an essential but minimal repertoire controlled by two Cullin scaffolds. A PfCullin1-linked CRL complex, recruiting a single substrate receptor, was identified as being required for parasite inner-membrane biogenesis and DNA replication. A second CRL complex functioning through a PfCullin4 scaffold was identified that utilised a previously unidentified adaptor protein and receptors to support DNA replication. These results show that the P. falciparum CRL complexes are essential in both nuclear maintenance and membrane integrity.https://doi.org/10.1038/s41598-025-05342-0MalariaE3 ligaseCullin-ring-ligaseP. falciparumUbiquitination |
| spellingShingle | Danushka Marapana Simon A. Cobbold Michal Pasternak Gerald J. Shami Stuart A. Ralph Sash Lopaticki Jumana Yousef Vineet Vaibhav Laura F. Dagley David Komander Alan F. Cowman Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexes Scientific Reports Malaria E3 ligase Cullin-ring-ligase P. falciparum Ubiquitination |
| title | Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexes |
| title_full | Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexes |
| title_fullStr | Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexes |
| title_full_unstemmed | Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexes |
| title_short | Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexes |
| title_sort | functional characterisation of components in two plasmodium falciparum cullin ring ligase complexes |
| topic | Malaria E3 ligase Cullin-ring-ligase P. falciparum Ubiquitination |
| url | https://doi.org/10.1038/s41598-025-05342-0 |
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