Pharmacological and toxicological investigations of cystobactamids reveal binding and inhibition of HCV entry receptor SCARB1
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Kidney, Hela Cell
SUBMITTER: 
Timo Risch
LAB HEAD: Rolf Müller
PROVIDER: PXD052895 | Pride | 2025-10-29
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| HEK293_Control.zip | Other | |||
| HEK293_competed.zip | Other | |||
| HEK293_enriched.zip | Other | |||
| HeLa_competed.zip | Other | |||
| HeLa_control.zip | Other |
Items per page: 5 1 - 5 of 7 |
Similar Datasets
Project description:Corramycin mode of action in Escherichia coli and mycobacterium tuberculosis. Proteome comparison of corramycin treated vs untreated bacterial protein expression
2026-08-13 | PXD060283 | Pride
Project description:the proteomic data of proteins of column and tentacle from Sea Anemone Heteractis magnifica
2026-09-10 | PXD081985 | Pride
Project description:The Periconia genus belongs to the phylum Ascomycota, order Pleosporales, family Periconiaceae. Periconia is widespread in many habitats but little is known about its ecology. Several species produce bioactive molecules, among them, Periconia digitata extracts were shown to be deadly active against the pine wilt nematode. The strain CNCM I-4278, here identified as P. digitata was able to inhibit the plant pathogen Phytophthora parasitica. Since P. digitata has great potential as biocontrol agent and the only other genome available in the Periconiaceae family is that of Periconia macrospinosa, which is quite fragmentary, we generated long-read genomic data for P. digitata. Thanks to the PacBio Hifi sequencing technology, we obtained a high-quality genome with a total length of 38,967,494 bp, represented by 13 haploid chromosomes. The transcriptomic and proteomic data strengthen and support the genome annotation. Besides representing a new reference genome within the Periconiaceae, this work will also contribute in our understanding of the Eukaryotic tree of life. Not least, opens new possibilities to the biotechnological use of the species.
2023-08-04 | PXD038112 | Pride
Project description:The Periconia genus belongs to the phylum Ascomycota, order Pleosporales, family Periconiaceae. Periconia is widespread in many habitats but little is known about its ecology. Several species produce bioactive molecules, among them, Periconia digitata extracts were shown to be deadly active against the pine wilt nematode. The strain CNCM I-4278, here identified as P. digitata was able to inhibit the plant pathogen Phytophthora parasitica. Since P. digitata has great potential as biocontrol agent and the only other genome available in the Periconiaceae family is that of Periconia macrospinosa, which is quite fragmentary, we generated long-read genomic data for P. digitata. Thanks to the PacBio Hifi sequencing technology, we obtained a high-quality genome with a total length of 38,967,494 bp, represented by 13 haploid chromosomes. The transcriptomic and proteomic data strengthen and support the genome annotation. Besides representing a new reference genome within the Periconiaceae, this work will also contribute in our understanding of the Eukaryotic tree of life. Not least, opens new possibilities to the biotechnological use of the species.
2023-08-04 | PXD038175 | Pride
Project description:Biflagellated zoospores enable plant pathogens of the Phytophthora genus to locate a host. While rhizospheric signals guiding zoospore movement toward roots are known, their membrane protein composition mediating these responses remains unclear. Here, we use LC-MS/MS to analyze membrane fractions from the flagella and cell bodies of Phytophthora parasitica zoospores, identifying major membrane protein classes and quantifying their subcellular distribution. These findings advance our understanding of protein-mediated dispersal and host targeting in zoospores andsupport the hypothesis that zoospores utilize polarized signal perception mechanisms for environmental sensing and movement.
2025-06-20 | PXD059087 | Pride
Project description:Lysine acetyltransferases (KATs) frequently cooperate with oncogenes such as c-Myc, estrogen receptor, and KMT2A-fusions to sustain malignant programs. Therapeutic targeting of KAT proteins has shown clinical efficacy, yet achieving homolog-selectivity for most KATs remains a major challenge. Here, by extending CRBN-based molecular glues beyond the canonical degron space, we develop a degrader of KAT2A exhibiting biochemical selectivity over all members of the KAT family. Cryo-EM structures reveal that CRBN engages KAT2A independent of a degron; instead, the molecular glue engages a surface-exposed tyrosine, mimicking antibody-like molecular recognition. Optimized molecular glues demonstrate that selective KAT2A degradation leads to potent ablation of H3K9Ac, antiproliferative effects in AML cell lines, and in vivo efficacy in a patient-derived xenograft model. Overall, these findings establish KAT2A as a targetable vulnerability, laying the foundation for the development of KAT2A-degrading molecular glues to treat a wide range of malignancies. More generally, the unanticipated binding mode suggests that CRBN-based molecular glues may be limited only by the accessible chemical diversity.
2026-08-29 | PXD072306 | Pride
Project description:Lysine acetyltransferases (KATs) frequently cooperate with oncogenes such as c-Myc, estrogen receptor, and KMT2A-fusions to sustain malignant programs. Therapeutic targeting of KAT proteins has shown clinical efficacy, yet achieving homolog-selectivity for most KATs remains a major challenge. Here, by extending CRBN-based molecular glues beyond the canonical degron space, we develop a degrader of KAT2A exhibiting biochemical selectivity over all members of the KAT family. Cryo-EM structures reveal that CRBN engages KAT2A independent of a degron; instead, the molecular glue engages a surface-exposed tyrosine, mimicking antibody-like molecular recognition. Optimized molecular glues demonstrate that selective KAT2A degradation leads to potent ablation of H3K9Ac, antiproliferative effects in AML cell lines, and in vivo efficacy in a patient-derived xenograft model. Overall, these findings establish KAT2A as a targetable vulnerability, laying the foundation for the development of KAT2A-degrading molecular glues to treat a wide range of malignancies. More generally, the unanticipated binding mode suggests that CRBN-based molecular glues may be limited only by the accessible chemical diversity.
2026-08-29 | PXD072361 | Pride
Project description:Lysine acetyltransferases (KATs) frequently cooperate with oncogenes such as c-Myc, estrogen receptor, and KMT2A-fusions to sustain malignant programs. Therapeutic targeting of KAT proteins has shown clinical efficacy, yet achieving homolog-selectivity for most KATs remains a major challenge. Here, by extending CRBN-based molecular glues beyond the canonical degron space, we develop a degrader of KAT2A exhibiting biochemical selectivity over all members of the KAT family. Cryo-EM structures reveal that CRBN engages KAT2A independent of a degron; instead, the molecular glue engages a surface-exposed tyrosine, mimicking antibody-like molecular recognition. Optimized molecular glues demonstrate that selective KAT2A degradation leads to potent ablation of H3K9Ac, antiproliferative effects in AML cell lines, and in vivo efficacy in a patient-derived xenograft model. Overall, these findings establish KAT2A as a targetable vulnerability, laying the foundation for the development of KAT2A-degrading molecular glues to treat a wide range of malignancies. More generally, the unanticipated binding mode suggests that CRBN-based molecular glues may be limited only by the accessible chemical diversity.
2026-08-29 | PXD072224 | Pride
Project description:Understanding the interplay of the proteome and the metabolome aids in understanding cellular phenotypes. To enable more robust inferences from such multi-omics analyses, combining proteomic and metabolomic datasets from the same sample provides major benefits by reducing technical variation between extracts during the pre-analytical phase, decreasing sample variation due to varying cellular content between aliquots, and limiting the required sample amount. We evaluated the advantages, practicality and feasibility of a single-sample workflow for combined proteome and metabolome analysis. In the workflow, termed MTBE-SP3, we combined a fully automated protein lysis and extraction protocol (autoSP3) with a semi-automated biphasic 75% EtOH/MTBE extraction for quantification of polar/non-polar metabolites. Additionally, we compared the resulting proteome of various biological matrices (FFPE tissue, fresh-frozen tissue, plasma, serum and cells) between autoSP3 and MTBE-SP3. Our analysis revealed that the single-sample workflow provided similar results to those obtained from autoSP3 alone, with an 85-98% overlap of proteins detected across the different biological matrices. Additionally, it provides distinct advantages by decreasing (tissue) heterogeneity by retrieving metabolomics and proteomic data from the identical biological material, and limiting the total amount of required material. Lastly, we applied MTBE-SP3 to a lung adenocarcinoma cohort of 10 patients. Integrating the metabolic and proteomic alterations between tumour and non-tumour adjacent tissue yielded consistent data independent of the method used. This revealed mitochondrial dysfunction in tumor tissue through deregulation of OGDH, SDH family enzymes and PKM. In summary, MTBE-SP3 enables the facile and confident parallel measurement of proteins and metabolites obtained from the same sample. This workflow is particularly applicable for studies with limited sample availability and offers the potential to enhance the integration of metabolomic and proteomic datasets.
2024-08-01 | PXD046035 | Pride
Project description:Single domain antibodies or antibody mimetics, such as monobodies, can be engineered to degrade undruggable targets via fusion to ubiquitin E3 ligases. In this study we developed multi-targeting biodegrader intrabodies by harnessing an inhibitor of apoptosis (IAP) E3 ligase RING domain, or the IAP-binding motif from SMAC/DIABLO. When fused with monobodies targeting the necroptotic death effector MLKL, IAP-binding intrabodies simultaneously targeted MLKL and IAPs for proteasomal degradation, thereby blocking necroptosis while sensitising cells to apoptosis. The potent degradative capacity of the IAP RING was demonstrated via its fusion to distinct antibody mimetics, with those targeting RAS enabling IAP and RAS proto-oncogenes to be concurrently eliminated. Quantitative proteomics identified that the anti-cancer potential of select IAP-binding intrabodies was due to their removal of the chromatin remodelling BAF complex. Consequently, we show that cancer cells exhibited IAP and BAF co-dependencies, with IAP RING intrabodies prolonging animal survival in an orthotopic breast cancer model. This work positions IAP-binding intrabodies as a novel class of biodegraders, with their multi-targeting capacity enabling the toggling of cell death modalities and eradication of cancer-drivers.
2026-03-03 | PXD061128 | Pride