Cullin-E ubiquitin ligase complex

cellstructuremech:cullin_e_ubiquitin_ligase_complex · Other · Multiprotein complex · Proposed

A cullin-RING protein complex defined by the Cullin-E scaffold, experimentally characterized in Trypanosoma brucei by co-isolation with Rbx1, Skp1.2 and kelch-domain proteins. The associated kelch proteins are candidate client-recognition subunits; simultaneous occupancy and fixed stoichiometry have not been established. [DOI:10.1038/s41598-025-32077-9]

UniProt location names: UniProt Consortium, CC BY 4.0. Reference label and route sources.

Components

Component	Type	Part of / acts on	Grounding	Genes	Essential	Role
Cullin-E scaffold subunit	Protein	part of	Reviewed label only (reviewed name; no accession asserted)	Cul-E	UNKNOWN	Defining cullin scaffold used as the affinity-isolation bait; its depletion disrupts coordination of organelle replication in the studied cells. `DOI:10.1038/s41598-025-32077-9` Table 1 and the Cullin-E Results identify Tb927.11.11430 as TbCul-E. Endogenously C-terminally 3xHA-tagged scaffold was immunoisolated from procyclic T. brucei; Supplementary Table S3, CULE row 2, confirms the bait locus. RNAi lethality does not establish assembly essentiality.
Rbx1 RING subunit	Protein	part of	Reviewed label only (reviewed name; no accession asserted)	Rbx1	UNKNOWN	Co-isolated RING-family constituent of the Cullin-E association; exact contacts and substrate-specific catalytic activity were not reconstituted. `DOI:10.1038/s41598-025-32077-9` Table 1, Figure 2B and Supplementary Table S3 CULE row 7 identify Tb927.10.1810 with the Cullin-E bait. The paper distinguishes this Rbx1 ortholog from the other Rbx-like paralogs; their family similarity does not make them additional Cullin-E constituents.
Skp1.2 adaptor subunit	Protein	part of	Reviewed label only (reviewed name; no accession asserted)	Skp1.2	UNKNOWN	Co-isolated Skp1-family constituent proposed to participate in adaptor recruitment; a direct binding or delivery mechanism remains unresolved. `DOI:10.1038/s41598-025-32077-9` Table 1, Figure 2B and Supplementary Table S3 CULE row 3 identify Tb927.9.8370 as the Skp1.2 constituent. This locus is distinct from the TUSK-associated SkpZ lineage, so the two complexes are not conflated.
kelch-domain client-recognition subunit	Protein	part of	Reviewed label only (reviewed name; no accession asserted)		UNKNOWN	Class representing four co-isolated kelch-domain proteins with proposed client-recognition roles, not four copies of a proven obligatory subunit or a claim that all four occupy one particle simultaneously. `DOI:10.1038/s41598-025-32077-9` The Cullin-E Results and Table 1 identify Tb927.8.6140, Tb927.11.11450, Tb927.5.1980 and Tb927.1.820 as kelch-domain proteins. All four have both significance flags in Supplementary Table S3 CULE rows 5, 10, 4 and 9 respectively, corroborating Figure 2B. Co-enrichment supports association but does not test exact stoichiometry or client recognition.

Canonical examples

NCBITaxon:5691 Trypanosoma brucei — Complex isolation used endogenously tagged procyclic-form Lister 427 cells. RNAi experiments are kept separate: Figure 6 depicts the bloodstream cell cycle and the qRT-PCR Methods name parental 2T1 cells, while the RNAi subsection does not explicitly restate stage and strain. The 927 protein database used for peptide annotation is not the cultured strain. The species taxon was verified at NCBI; no broad clade-level assembly distribution is inferred. [DOI:10.1038/s41598-025-32077-9]

Functions

coordination of organelle replication — Cullin-E RNAi in the studied T. brucei cells produces an increasing fraction with one kinetoplast and two nuclei (1K2N); imaged 1K2N cells also retain a single Golgi apparatus. This supports a role in coordinating division events, but does not identify the molecular pathway or demonstrate that any affected protein is a direct ligase substrate.
- DOI:10.1038/s41598-025-32077-9 The paper's own Cullin-E knockdown Results and Figure 6B-D provide DAPI counts and GRASP immunofluorescence. The function is bounded to these observations, not the paper's conflicted attribution of older WDR1/PLK work to Cullin-E.

Mechanism graphs

Measured outputs of Cullin-E depletion (FUNCTION)

Source-bounded RNAi phenotypes and abundance changes, not a reconstructed ligase or organelle-replication mechanism.

Subject	Predicate	Object	Evidence
Cullin-E RNAi induction	decreases abundance of	Cullin-E scaffold subunit	`DOI:10.1038/s41598-025-32077-9` Figure 7 shows the Cullin-E point on the decreased-abundance side of the 24-hour LFQ comparison (three induced and three uninduced samples).
Cullin-E RNAi induction	increases	1K2N cell fraction	`DOI:10.1038/s41598-025-32077-9` Figure 6B-C shows DAPI-stained 1K2N cells and counts of more than 300 cells per time point. Rounded pie-chart percentages are not reinterpreted as exact unrounded counts or mechanistic transition rates.
Cullin-E RNAi induction	yields cells displaying	single Golgi in imaged 1K2N cells	`DOI:10.1038/s41598-025-32077-9` Cullin-E knockdown Results and Figure 6D report a single Golgi in 1K2N cells. GRASP and MitoTracker are phenotype markers, not localization of the Cullin-E complex.
Cullin-E RNAi induction	increases	whole-cell KKT9 abundance	`DOI:10.1038/s41598-025-32077-9` Figure 7 point 7 and the Cullin-E knockdown Results identify increased KKT9, Tb927.8.1150, in whole-cell LFQ proteomics.
Cullin-E RNAi induction	decreases	whole-cell Tb927.10.8810 abundance	`DOI:10.1038/s41598-025-32077-9` Figure 7 point 8 and the Cullin-E knockdown Results identify this decreased protein. Its reported basal-body association is not used to infer Cullin-E localization or a direct substrate relationship.

Discussions

CURATION_TODO (RESOLVED): Keep the Cullin-E association distinct from other cullins and TUSK. A scaffold name or broader ligase class is not an exact complex identity.
CURATION_TODO (OPEN): Resolve exact source-neutral families for the four component classes. Broad domains or family matches cannot establish exact paralog membership.
CURATION_TODO (RESOLVED): Exclude the older WDR1-DDB1-PLK mechanism from Cullin-E. The newer paper's citation attribution conflicts with the cited primary identifiers.
CURATION_TODO (OPEN): Establish simultaneous composition, localization and direct ligase substrates. Affinity enrichment and RNAi abundance changes do not reconstruct a molecular mechanism.
CURATION_TODO (RESOLVED): Keep uncertain enrichment hits and modifiers separate from established constituent classes. Not every affinity-isolation hit is a stable structural constituent or client.
CURATION_TODO (OPEN): Reconcile RNAi specimen detail, control counts and the duplicate Figure 7 locus. Source-specific descriptions must not be silently harmonized.
CURATION_TODO (OPEN): Obtain experimentally resolved imaging of the assembled Cullin-E complex. Phenotype images and generic or predicted models do not locate or resolve this assembly.

Datasets

Trypanosome cullin isolation and depletion proteomics (PXD042022) · PRIDE · PROTEOMICS
Organism: Trypanosoma brucei
Native accession, organism 5691, DOI and PMID:41413177 verified. The native entry is a PARTIAL submission. It describes three tagged isolations and six wild-type controls, whereas the paper's Methods and Supplementary Table S3 list seven wild-type controls. Cullin-E RNAi uses label-free proteomics at 12 and 24 hours; the separate Cullin-A experiment uses SILAC. No raw spectra, processed table or bulk repository text is redistributed. Published Supplementary Table S3 was inspected read-only.

Evidence

DOI:10.1038/s41598-025-32077-9 Canavate del Pino et al., PMID:41413177. Current PMC12816148.1 JATS identity and checksum verified; Table 1, composition and knockdown Results, Discussion and relevant Methods inspected. Original Figures 2, 6 and 7 visually inspected with native media checksum verification. Supplementary Table S3 CULE identifiers and enrichment flags independently inspected. Supports the named complex and bounded perturbation outputs, not fixed architecture or the asserted older WDR1/PLK mechanism.
DOI:10.1371/journal.ppat.1006146 PMID:28052114, native PMC5241021.1. The older Results and Figure 3 assign the WDR1-DDB1 association to TbCUL4, Tb927.3.1290, and report that TbCUL1, Tb927.11.11430, did not co-precipitate WDR1. This establishes the cross-paper identity conflict; it is not evidence for a WDR1/PLK mechanism in Cullin-E.

Curation history

2026-10-04T18:55:03Z codex · CREATED_RECORD — Scaffolded by scripts/new_record.py
2026-10-04T18:56:49Z codex · CURATED_RECORD — Added four source-bounded constituent classes, verified broad GO parent, studied Trypanosoma example, organelle-replication function, nonmechanistic RNAi graph and PRIDE link. Preserved control/stage/locus discrepancies; excluded the misattributed older WDR1-PLK mechanism and unsupported stoichiometry, family mappings, substrates and assembly imaging.

Source: data/structures/other/cullin_e_ubiquitin_ligase_complex.yaml