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

• DOI: 10.1371/journal.ppat.1012336
• Publication Date: 2024-07-17T17:36:05Z
• Authors: Camila Rolemberg ...; Caroline Torres; Ellen Gomes; Giovana Maffei Ro...; Wesley Klaysson P...; Nayore Tamie Taka...; Luana Aparecida R...; Iran Malavazi; Marcelo Damário G...; Jeziel Dener Dama...; Vitor Luiz da Silva; Marcos Antonio Fe...; Marcelo Santos da...; Alessandro Silva ...; Adriano Cappellaz...; Sandra Regina Mar...; Felipe Roberti Te...
• Keywords: Cullin; Skp1; F-box protein; Protein Degradation

Cullin-1-RING ubiquitin ligases (CRL1) or SCF1 (SKP1-CUL1-RBX1) E3 are the largest and most extensively investigated class of in mammals that regulate fundamental processes, such as cell cycle proliferation. These enzymes multiprotein complexes comprising SKP1, CUL1, RBX1, an F-box protein acts a specificity factor by interacting with SKP1 through its domain recruiting substrates via other domains. important players ubiquitination process, recognizing transferring to destined for degradation proteasomes processing deubiquitinating enzymes. The ubiquitin-proteasome system (UPS) is main regulator intracellular proteolysis eukaryotes required parasites alternate hosts their life cycles, resulting successful parasitism. Leishmania UPS poorly investigated, CRL1 L . infantum , causative agent visceral leishmaniasis Latin America, yet be described. Here, we show genes LINF_110018100 (SKP1-like protein), LINF_240029100 (cullin-like protein-like LINF_210005300 (ring-box 1 –putative) form LinfCRL1 complex structurally similar H sapiens CRL1. Mass spectrometry analysis LinfSkp1 LinfCul1 interactomes revealed proteins involved several including six known F-box-like (Flp) (data available ProteomeXchange identifier PXD051961). interaction LinfFlp 1–6 was confirmed, using vitro assays, demonstrated function LinfCRL1(Flp1) transfer ubiquitin. We also found LinfSKP1 LinfRBX1 knockouts resulted nonviable lineages, whereas LinfCUL1 parasite growth rosette formation. Finally, our results suggest regulates S phase progression possibly transition between late G2 Thus, new has been described functions related various parasitic processes may serve prospective targets treatment.