ArticlePLoS pathogens2008
Structural and biochemical bases for the inhibition of autophagy and apoptosis by viral BCL-2 of murine gamma-herpesvirus 68.
Article in PLoS pathogens, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.
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Who cites it
131 citing papers in PubMed, 188 citations in OpenAlex.
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- Engineered exosomes deliver structurally optimized toad BAX to reactivate mitochondrial apoptosis in colorectal cancer.Frontiers in oncology · 2026Article
- Training bias and sequence alignments shape protein-peptide docking by AlphaFold and related methods.Protein science : a publication of the Protein Society · 2025Article
- Dynamic regulation of autophagy during Semliki Forest virus infection of neuroblastoma cells.The Journal of general virology · 2025Article
- Structural insights into Beclin 1 interactions with it's regulators for autophagy modulation.Computational and structural biotechnology journal · 2025Review
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- Invariant BECN1 CXXC motifs bind ZnAutophagy · 2024Article
- A simple method for developing lysine targeted covalent protein reagents.Nature communications · 2023Article
- Epstein-Barr Virus Encoded BCL2, BHRF1, Downregulates Autophagy by Noncanonical Binding of BECN1.Biochemistry · 2023Article
- Structural basis for proapoptotic activation of Bak by the noncanonical BH3-only protein Pxt1.PLoS biology · 2023Article
- Apoptosis and Phagocytosis as Antiviral Mechanisms.Sub-cellular biochemistry · 2023Article
- Impact of PIN1 Inhibition on Tumor Progression and Chemotherapy Sensitivity in Colorectal Cancer.Journal of gastrointestinal cancer · 2022Article
- Structure-based assessment and druggability classification of protein-protein interaction sites.Scientific reports · 2022Article
- Structural Insight into KsBcl-2 Mediated Apoptosis Inhibition by Kaposi Sarcoma Associated Herpes Virus.Viruses · 2022Article
- Autophagy Modulators in Coronavirus Diseases: A Double Strike in Viral Burden and Inflammation.Frontiers in cellular and infection microbiology · 2022Review
- The Multi-Faceted Role of Autophagy During Animal Virus Infection.Frontiers in cellular and infection microbiology · 2022Review
- Targeting Selective Autophagy as a Therapeutic Strategy for Viral Infectious Diseases.Frontiers in microbiology · 2022Review
71 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
All gammaherpesviruses express homologues of antiapoptotic B-cell lymphoma-2 (BCL-2) to counter the clearance of infected cells by host antiviral defense machineries. To gain insights into the action mechanisms of these viral BCL-2 proteins, we carried out structural and biochemical analyses on the interactions of M11, a viral BCL-2 of murine gamma-herpesvirus 68, with a fragment of proautophagic Beclin1 and BCL-2 homology 3 (BH3) domain-containing peptides derived from an array of proapoptotic BCL-2 family proteins. Mainly through hydrophobic interactions, M11 bound the BH3-like domain of Beclin1 with a dissociation constant of 40 nanomole, a markedly tighter affinity compared to the 1.7 micromolar binding affinity between cellular BCL-2 and Beclin1. Consistently, M11 inhibited autophagy more efficiently than BCL-2 in NIH3T3 cells. M11 also interacted tightly with a BH3 domain peptide of BAK and those of the upstream BH3-only proteins BIM, BID, BMF, PUMA, and Noxa, but weakly with that of BAX. These results collectively suggest that M11 potently inhibits Beclin1 in addition to broadly neutralizing the proapoptotic BCL-2 family in a similar but distinctive way from cellular BCL-2, and that the Beclin1-mediated autophagy may be a main target of the virus.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.