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Functional characterisation of Cullin-Ring-Ligases in Plasmodium falciparum

ABSTRACT: Ubiquitination is the key post-translational modification in eukaryotic cells that governs protein degradation, localisation, and activity. This process results in the tagging of ubiquitin to protein substrates by a concerted enzyme cascade of E1, E2 and E3 enzymes. The largest superfamily of these proteins includes the Cullin-Ring-Ligase (CRL) complexes of E3 ligases. 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 E3 ligases were characterised to reveal an essential but minimal repertoire controlled by two Cullin scaffolds. A PfCullin1-linked CRL complex was identified as being required for parasite inner-membrane biogenesis and DNA replication. This complex recruits only one substrate receptor, compared to the ~70 receptors used interchangeably by human cells. 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 E3 ubiquitin ligases play an essential role in the biology of this important infectious agent.

INSTRUMENT(S): Orbitrap Eclipse, timsTOF Pro

ORGANISM(S): Plasmodium Falciparum (isolate 3d7)

TISSUE(S): Blood

DISEASE(S): Plasmodium Falciparum Malaria

SUBMITTER: Laura Dagley

LAB HEAD: Prof. Alan Cowman

PROVIDER: PXD063957 | Pride | 2025-07-11

REPOSITORIES: Pride

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			Action	DRS
	DIANN_P4327.zip	Other
	DIANN_P4762.zip	Other
	DIANN_P5229_Danu_Global.zip	Other
	GID1_1.zip	Other
	GID1_2.zip	Other

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