Evidence map›Paper›PMID 42523352›Full record

ArticlebioRxiv : the preprint server for biology2026

Retrograde trafficking inhibitors allosterically trap Get3 to block tail-anchored protein biogenesis.

Juliet A Lee, Xilin Gu, Charlene Chan, Vida Storm Robertson, Victor Garcia-Ruiz, Yancheng E Li, Anna Huyen Ngo, Philip Alabi, Vladimir Denic, Jason K Sello and 1 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Juliet A LeeDivision of Chemistry and Chemical Engineering, California Institute of Technology; Pasadena, CA 91125, USA.ORCID 0000-0001-5207-515X
Xilin GuDivision of Pharmaceutical Chemistry, University of California, San Francisco; San Francisco, CA 94143, USA.ORCID 0000-0002-5441-7958
Charlene ChanDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0002-0479-3373
Vida Storm RobertsonDivision of Chemistry and Chemical Engineering, California Institute of Technology; Pasadena, CA 91125, USA.ORCID 0000-0002-8130-051X
Victor Garcia-RuizDivision of Chemistry and Chemical Engineering, California Institute of Technology; Pasadena, CA 91125, USA.ORCID 0009-0008-8358-3104
Yancheng E LiDivision of Chemistry and Chemical Engineering, California Institute of Technology; Pasadena, CA 91125, USA.ORCID 0000-0002-7110-2448
Anna Huyen NgoDivision of Chemistry and Chemical Engineering, California Institute of Technology; Pasadena, CA 91125, USA.ORCID 0009-0000-3827-3846
Philip AlabiDivision of Pharmaceutical Chemistry, University of California, San Francisco; San Francisco, CA 94143, USA.ORCID 0000-0003-3976-2179
Vladimir DenicDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0002-1982-7281
Jason K SelloDivision of Pharmaceutical Chemistry, University of California, San Francisco; San Francisco, CA 94143, USA.ORCID 0000-0001-6263-7902
William M ClemonsDivision of Chemistry and Chemical Engineering, California Institute of Technology; Pasadena, CA 91125, USA.ORCID 0000-0002-0021-889X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Retro-1 and Retro-2 are structurally distinct small molecules that protect cells from diverse toxins and viruses by disrupting retrograde trafficking, yet their mechanism of action has remained elusive. We show that both compounds target Get3, the ATPase chaperone of the guided entry of tail-anchored proteins (GET) pathway, which mediates biogenesis of tail-anchored SNARE proteins required for retrograde transport to the ER membrane. Cryo-electron microscopy reveals that Retro compounds bind a cryptic pocket in Get3, allosterically stabilizing Get3 in a stalled complex with upstream pathway components. Our work uncovers the GET pathway as an unsuspected vulnerability in pathogen entry, provides clear routes toward compound optimization, and establishes stabilization of dynamic protein complexes as a therapeutic strategy.

Identifiers

PMID42523352
PMCPMC13404970

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.