Functional characterization of Cullin-1-RING ubiquitin ligase (CRL1) complex in Leishmania infantum.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39018347", "kind": "science-record", "revision": 3, "content_hash": "sha256:c0cb8dce37520ed01c6566d448c1ee9e26484c3143fe168f9583620f6e7d0af8", "created_at": "2026-11-01T20:29:05Z", "updated_at": "2026-11-01T22:12:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Functional characterization of Cullin-1-RING ubiquitin ligase (CRL1) complex in Leishmania infantum.", "doi": "10.1371/journal.ppat.1012336", "pmid": "39018347", "authors": ["Camila Rolemberg Santana Travaglini Berti de Correia", "Caroline Torres", "Ellen Gomes", "Giovana Maffei Rodriguez", "Wesley Klaysson Pereira Regatieri", "Nayore Tamie Takamiya", "Luana Aparecida Rogerio", "Iran Malavazi", "Marcelo Damário Gomes", "Jeziel Dener Damasceno", "Vitor Luiz da Silva", "Marcos Antonio Fernandes de Oliveira", "Marcelo Santos da Silva", "Alessandro Silva Nascimento", "Adriano Cappellazzo Coelho", "Sandra Regina Maruyama", "Felipe Roberti Teixeira"], "journal": "PLoS pathogens", "year": 2024, "abstract": "Cullin-1-RING ubiquitin ligases (CRL1) or SCF1 (SKP1-CUL1-RBX1) E3 ubiquitin ligases are the largest and most extensively investigated class of E3 ligases in mammals that regulate fundamental processes, such as the cell cycle and proliferation. These enzymes are multiprotein complexes comprising SKP1, CUL1, RBX1, and an F-box protein that acts as a specificity factor by interacting with SKP1 through its F-box domain and recruiting substrates via other domains. E3 ligases are important players in the ubiquitination process, recognizing and transferring ubiquitin to substrates destined for degradation by proteasomes or processing by deubiquitinating enzymes. The ubiquitin-proteasome system (UPS) is the main regulator of intracellular proteolysis in eukaryotes and is required for parasites to alternate hosts in their life cycles, resulting in successful parasitism. Leishmania UPS is poorly investigated, and CRL1 in L. infantum, the causative agent of visceral leishmaniasis in Latin America, is yet to be described. Here, we show that the L. infantum genes LINF_110018100 (SKP1-like protein), LINF_240029100 (cullin-like protein-like protein), and LINF_210005300 (ring-box protein 1 -putative) form a LinfCRL1 complex structurally similar to the H. sapiens CRL1. Mass spectrometry analysis of the LinfSkp1 and LinfCul1 interactomes revealed proteins involved in several intracellular processes, including six F-box proteins known as F-box-like proteins (Flp) (data are available via ProteomeXchange with identifier PXD051961). The interaction of LinfFlp 1-6 with LinfSkp1 was confirmed, and using in vitro ubiquitination assays, we demonstrated the function of the LinfCRL1(Flp1) complex to transfer ubiquitin. We also found that LinfSKP1 and LinfRBX1 knockouts resulted in nonviable L. infantum lineages, whereas LinfCUL1 was involved in parasite growth and rosette formation. Finally, our results suggest that LinfCul1 regulates the S phase progression and possibly the transition between the late S to G2 phase in L. infantum. Thus, a new class of E3 ubiquitin ligases has been described in L. infantum with functions related to various parasitic processes that may serve as prospective targets for leishmaniasis treatment.", "claims": [{"id": "claim-method", "statement": "Phylogenetic reconstruction of each gene was performed with Maximum Likelihood (ML) method [86] using MEGA (version 11) and Bayesian Inference (BI) method using BEAST (version 1.10.4) [33]. For ML method the reliability of the obtained phylogeny was subsequently evaluated using the statistical bootstrap method [87], using a minimum of 1000 replicates.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39018347", "locator": "sections[22] \"Phylogenetic analysis\" paragraph 2", "quote": "Phylogenetic reconstruction of each gene was performed with Maximum Likelihood (ML) method [86] using MEGA (version 11) and Bayesian Inference (BI) method using BEAST (version 1.10.4) [33]. For ML method the reliability of the obtained phylogeny was subsequently evaluated using the statistical bootstrap method [87], using a minimum of 1000 replicates."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Mass spectrometry analysis of the LinfSkp1 and LinfCul1 interactomes revealed proteins involved in several intracellular processes, including six F-box proteins known as F-box-like proteins (Flp) (data are available via ProteomeXchange with identifier PXD051961).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39018347", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Mass spectrometry analysis of the LinfSkp1 and LinfCul1 interactomes revealed proteins involved in several intracellular processes, including six F-box proteins known as F-box-like proteins (Flp) (data are available via ProteomeXchange with identifier PXD051961)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The L. infantum genes LINF_110018100, LINF_240029100, and LINF_210005300 form a LinfCRL1 complex structurally similar to the H. sapiens CRL1 complex.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39018347", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Here, we show that the L. infantum genes LINF_110018100 (SKP1-like protein), LINF_240029100 (cullin-like protein-like protein), and LINF_210005300 (ring-box protein 1 –putative) form a LinfCRL1 complex structurally similar to the H. sapiens CRL1."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The L. infantum genes LINF_110018100, LINF_240029100, and LINF_210005300 form a LinfCRL1 complex structurally similar to the H. sapiens CRL1 complex.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39018347"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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