ArticlePLoS computational biology2014
Genome-wide prediction and validation of peptides that bind human prosurvival Bcl-2 proteins.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Inhibition of BAK-mediated apoptosis by the BH3-only protein BNIP5.Cell death and differentiation · 2025Article
- Learning the language of antibody hypervariability.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Design of cross-reactive antigens with machine learning and high-throughput experimental evaluation.Frontiers in bioinformatics · 2025Article
- Surfaces: a software to quantify and visualize interactions within and between proteins and ligands.Bioinformatics (Oxford, England) · 2023Article
- Structural basis for proapoptotic activation of Bak by the noncanonical BH3-only protein Pxt1.PLoS biology · 2023Article
- Rapid Evaluation of Staple Placement in Stabilized α Helices Using Bacterial Surface Display.ACS chemical biology · 2023Article
- Peptides from human BNIP5 and PXT1 and non-native binders of pro-apoptotic BAK can directly activate or inhibit BAK-mediated membrane permeabilization.Structure (London, England : 1993) · 2023Article
- Editorial: In celebration of women in science: Structural biology.Frontiers in molecular biosciences · 2023Article
- Dual RNA Sequencing Reveals Key Events When DifferentFrontiers in cellular and infection microbiology · 2022Article
- Structural Details of BH3 Motifs and BH3-Mediated Interactions: an Updated Perspective.Frontiers in molecular biosciences · 2022Review
- Deep geometric representations for modeling effects of mutations on protein-protein binding affinity.PLoS computational biology · 2021Article
- Alterations of the interactome of Bcl-2 proteins in breast cancer at the transcriptional, mutational and structural level.PLoS computational biology · 2019Article
- Tertiary Structural Motif Sequence Statistics Enable Facile Prediction and Design of Peptides that Bind Anti-apoptotic Bfl-1 and Mcl-1.Structure (London, England : 1993) · 2019Article
- Peptide design by optimization on a data-parameterized protein interaction landscape.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Enriching Peptide Libraries for Binding Affinity and Specificity Through Computationally Directed Library Design.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Designing helical peptide inhibitors of protein-protein interactions.Current opinion in structural biology · 2016Review
- Rapid Optimization of Mcl-1 Inhibitors using Stapled Peptide Libraries Including Non-Natural Side Chains.ACS chemical biology · 2016Article
- Mitochondria-Judges and Executioners of Cell Death Sentences.Molecular cell · 2016Review
- AB-Bind: Antibody binding mutational database for computational affinity predictions.Protein science : a publication of the Protein Society · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Programmed cell death is regulated by interactions between pro-apoptotic and prosurvival members of the Bcl-2 family. Pro-apoptotic family members contain a weakly conserved BH3 motif that can adopt an alpha-helical structure and bind to a groove on prosurvival partners Bcl-xL, Bcl-w, Bcl-2, Mcl-1 and Bfl-1. Peptides corresponding to roughly 13 reported BH3 motifs have been verified to bind in this manner. Due to their short lengths and low sequence conservation, BH3 motifs are not detected using standard sequence-based bioinformatics approaches. Thus, it is possible that many additional proteins harbor BH3-like sequences that can mediate interactions with the Bcl-2 family. In this work, we used structure-based and data-based Bcl-2 interaction models to find new BH3-like peptides in the human proteome. We used peptide SPOT arrays to test candidate peptides for interaction with one or more of the prosurvival proteins Bcl-xL, Bcl-w, Bcl-2, Mcl-1 and Bfl-1. For the 36 most promising array candidates, we quantified binding to all five human receptors using direct and competition binding assays in solution. All 36 peptides showed evidence of interaction with at least one prosurvival protein, and 22 peptides bound at least one prosurvival protein with a dissociation constant between 1 and 500 nM; many peptides had specificity profiles not previously observed. We also screened the full-length parent proteins of a subset of array-tested peptides for binding to Bcl-xL and Mcl-1. Finally, we used the peptide binding data, in conjunction with previously reported interactions, to assess the affinity and specificity prediction performance of different models.
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Registered trials
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.