ArticleThe Journal of biological chemistry2014
The functional differences between pro-survival and pro-apoptotic B cell lymphoma 2 (Bcl-2) proteins depend on structural differences in their Bcl-2 homology 3 (BH3) domains.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- A proteome-wide dependency map of protein interaction motifs.Nature structural & molecular biology · 2026Article
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- Review
- Structural Details of BH3 Motifs and BH3-Mediated Interactions: an Updated Perspective.Frontiers in molecular biosciences · 2022Review
- Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3NPJ breast cancer · 2021Article
- Diversity in the intrinsic apoptosis pathway of nematodes.Communications biology · 2020Article
- BCL-w: apoptotic and non-apoptotic role in health and disease.Cell death & disease · 2020Review
- Photocatalytic proximity labelling of MCL-1 by a BH3 ligand.Communications chemistry · 2019Article
- Bioinformatic identification and expression analysis of the chicken B cell lymphoma (BCL) gene.Genes & genomics · 2019Article
- The Structural Biology of Bcl-xInternational journal of molecular sciences · 2019Review
- Structural insights into BCL2 pro-survival protein interactions with the key autophagy regulator BECN1 following phosphorylation by STK4/MST1.Autophagy · 2019Article
- Rapid Mapping of Protein Interactions Using Tag-Transfer Photocrosslinkers.Angewandte Chemie (International ed. in English) · 2018Article
- The deadly landscape of pro-apoptotic BCL-2 proteins in the outer mitochondrial membrane.The FEBS journal · 2016Review
- TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL.Scientific reports · 2016Article
- The BECN1 N-terminal domain is intrinsically disordered.Autophagy · 2016Article
- Role of gga-miR-221 and gga-miR-222 during Tumour Formation in Chickens Infected by Subgroup J Avian Leukosis Virus.Viruses · 2015Article
- Redefining the BH3 Death Domain as a 'Short Linear Motif'.Trends in biochemical sciences · 2015Review
- Locating Herpesvirus Bcl-2 Homologs in the Specificity Landscape of Anti-Apoptotic Bcl-2 Proteins.Journal of molecular biology · 2015Article
- Crystal structure of Bax bound to the BH3 peptide of Bim identifies important contacts for interaction.Cell death & disease · 2015Article
- Structural transition in Bcl-xL and its potential association with mitochondrial calcium ion transport.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bcl-2 homology 3 (BH3) domains are short sequence motifs that mediate nearly all protein-protein interactions between B cell lymphoma 2 (Bcl-2) family proteins in the intrinsic apoptotic cell death pathway. These sequences are found on both pro-survival and pro-apoptotic members, although their primary function is believed to be associated with induction of cell death. Here, we identify critical features of the BH3 domains of pro-survival proteins that distinguish them functionally from their pro-apoptotic counterparts. Biochemical and x-ray crystallographic studies demonstrate that these differences reduce the capacity of most pro-survival proteins to form high affinity "BH3-in-groove" complexes that are critical for cell death induction. Switching these residues for the corresponding residues in Bcl-2 homologous antagonist/killer (Bak) increases the binding affinity of isolated BH3 domains for pro-survival proteins; however, their exchange in the context of the parental protein causes rapid proteasomal degradation due to protein destabilization. This is supported by further x-ray crystallographic studies that capture elements of this destabilization in one pro-survival protein, Bcl-w. In pro-apoptotic Bak, we demonstrate that the corresponding distinguishing residues are important for its cell-killing capacity and antagonism by pro-survival proteins.
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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.