Evidence map›Paper›PMID 40911686›Full record

ArticleScience advances2025

Computational design of potent and selective binders of BAK and BAX.

Stephanie Berger, Erinna F Lee, Tiffany J Harris, Sharon Tran, Asim K Bera, Lauren Arguinchona, Alex Kang, Banumathi Sankaran, Sila Kasapgil, Michelle S Miller and 9 more

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Stephanie BergerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0002-3738-5907
Erinna F LeeDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Sciences, La Trobe University, Melbourne, VIC 3086, Australia.
Tiffany J HarrisOlivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.
Sharon TranOlivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.ORCID 0000-0003-1321-5556
Asim K BeraDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0001-9473-2912
Lauren ArguinchonaDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0001-5935-4549
Alex KangDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0001-5487-0499
Banumathi SankaranMolecular Biophysics and Integrated Bioimaging, Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.ORCID 0000-0002-3266-8131
Sila KasapgilWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.
Michelle S MillerWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.ORCID 0000-0003-1972-4503
Sean SmythWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.ORCID 0000-0002-4227-4216
Mariam LutfiWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.
Rachel T UrenWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.ORCID 0000-0001-7456-478X
Ruth M KluckWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.ORCID 0000-0002-7101-1925
Peter M ColmanWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.
Walter D FairlieDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Sciences, La Trobe University, Melbourne, VIC 3086, Australia.
Peter E CzabotarWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.ORCID 0000-0002-2594-496X
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0001-7896-6217
Richard W BirkinshawWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.ORCID 0000-0003-1825-0182

Funding

User Training and OutreachP30GM124169 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI PAUL David ADAMS, Gregory L Hura · 2017 to 2026
$28.6M
TrainingP41GM103533 · NIGMS · UNIVERSITY OF WASHINGTON · PI YATES III, JOHN R · 2012 to 2021
$20.7M
Design of de novo interleukin mimics for targeted immunotherapyR01CA240339 · NCI · UNIVERSITY OF WASHINGTON · PI BAKER, DAVID · 2019 to 2023
$2.1M
A Pixel Array Detector System for Small Angle X-ray ScatteringS10OD018483 · OD · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI CLASSEN, SCOTT · 2014 to 2014
$998k
NCI NIH HHS R01 CA240339NIGMS NIH HHS P30 GM124169NIGMS NIH HHS P41 GM103533NIH HHS S10 OD018483
6 · The paper itself

Abstract

Potent and selective binders of the key proapoptotic proteins BAK and BAX have not been described. We use computational protein design to generate high affinity binders of BAK and BAX with greater than 100-fold specificity for their target. Both binders activate their targets when at low concentration, driving pore formation, but inhibit membrane permeabilization when in excess. Crystallography shows that the BAK binder induces BAK unfolding, exposing the α6 helix and BH3 domain. Together, these data suggest that upon binding, BAK or BAX unfold; at high binder concentrations, self-association of the partially folded BAK or BAX proteins is blocked and the membrane remains intact, whereas at low concentrations, dimers form, and the membrane ruptures. Our designed binders modulate apoptosis via direct, specific interactions with BAK and BAX and reveal that for therapeutic strategies targeting BAK and BAX, inhibition requires saturating binder concentrations at the site of action.

Indexed as

bcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinApoptosisHumansModels, MolecularProtein BindingBAK1 protein, humanbcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer Protein

Identifiers

PMID40911686
PMCPMC12412652

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LicenceCC BY
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Registered trials

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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.