ArticleScience advances2021
De novo macrocyclic peptides for inhibiting, stabilizing, and probing the function of the retromer endosomal trafficking complex.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
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Who cites it
16 citing papers in PubMed.
- EhVps29 Has a Role in the Location of the Retromer Complex and the Function of Key Virulence Factors inMicroorganisms · 2026Article
- Dystonia-predominant VPS35-related parkinson's disease: diagnostic challenges and the role of Levodopa response in unmasking genetic etiology.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation.Nature communications · 2025Article
- Identification of a VPS29 isoform with restricted association to Retriever and Retromer accessory proteins through autoinhibition.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular basis for the assembly of the Vps5-Vps17 SNX-BAR proteins with Retromer.Nature communications · 2025Article
- De novo discovery of a molecular glue-like macrocyclic peptide that induces MCL1 homodimerization.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- VPS35-Retromer: Multifunctional Roles in Various Biological Processes - A Focus on Neurodegenerative Diseases and Cancer.Journal of inflammation research · 2025Review
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- Assembly and fission of tubular carriers mediating protein sorting in endosomes.Nature reviews. Molecular cell biology · 2024Review
- Structural basis for coupling of the WASH subunit FAM21 with the endosomal SNX27-Retromer complex.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Type I gamma phosphatidylinositol phosphate 5-kinase i5 controls cell sensitivity to interferon.Developmental cell · 2024Article
- The Entamoeba histolytica Vps26 (EhVps26) retromeric protein is involved in phagocytosis: Bioinformatic and experimental approaches.PloS one · 2024Article
- Pharmacologic enhancement of retromer rescues endosomal pathology induced by defects in the Alzheimer's gene SORL1.Stem cell reports · 2023Article
- Article
- Receptor Recycling by Retromer.Molecular and cellular biology · 2023Review
- Understanding the contributions of VPS35 and the retromer in neurodegenerative disease.Neurobiology of disease · 2022Review
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
The retromer complex (Vps35-Vps26-Vps29) is essential for endosomal membrane trafficking and signaling. Mutation of the retromer subunit Vps35 causes late-onset Parkinson’s disease, while viral and bacterial pathogens can hijack the complex during cellular infection. To modulate and probe its function, we have created a novel series of macrocyclic peptides that bind retromer with high affinity and specificity. Crystal structures show that most of the cyclic peptides bind to Vps29 via a Pro-Leu–containing sequence, structurally mimicking known interactors such as TBC1D5 and blocking their interaction with retromer in vitro and in cells. By contrast, macrocyclic peptide RT-L4 binds retromer at the Vps35-Vps26 interface and is a more effective molecular chaperone than reported small molecules, suggesting a new therapeutic avenue for targeting retromer. Last, tagged peptides can be used to probe the cellular localization of retromer and its functional interactions in cells, providing novel tools for studying retromer function.
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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.