ArticleNature communications2024
Allosteric control of dynamin-related protein 1 through a disordered C-terminal Short Linear Motif.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- AGPAT2 acts at the crossroads of lipid biosynthesis and DRP1-mediated ER morphogenesis.Nature communications · 2025Article
- The intermediate filament protein GFAP regulates mitochondrial fission in astrocytes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Gipc3 Mutation Might Cause Sensorineural Hearing Loss by Inhibiting Mitophagy in Inner Ear Hair Cells.Molecular neurobiology · 2025Article
- Conformational Rearrangement of Fission DSPs.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Second-order allosteric control as a mechanism for compensatory mutations in B-cell translocation gene 2.Protein science : a publication of the Protein Society · 2025Article
- Drp1 Proteins Released from Hydrolysis-Driven Scaffold Disassembly Trigger Nucleotide-Dependent Membrane Remodeling to Promote Scission.Journal of the American Chemical Society · 2025Article
- Mitochondrial fission - changing perspectives for future progress.Journal of cell science · 2025Review
- Nanoscale dynamics of Dynamin 1 helices reveals squeeze-twist deformation mode critical for membrane fission.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Selection of Nucleotide-Encoded Mass Libraries of Macrocyclic Peptides for Inaccessible Drug Targets.Chemical reviews · 2024Review
- ROS-mediated cytoplasmic localization of CARM1 induces mitochondrial fission through DRP1 methylation.Redox biology · 2024Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
The mechanochemical GTPase dynamin-related protein 1 (Drp1) catalyzes mitochondrial and peroxisomal fission, but the regulatory mechanisms remain ambiguous. Here we find that a conserved, intrinsically disordered, six-residue Short Linear Motif at the extreme Drp1 C-terminus, named CT-SLiM, constitutes a critical allosteric site that controls Drp1 structure and function in vitro and in vivo. Extension of the CT-SLiM by non-native residues, or its interaction with the protein partner GIPC-1, constrains Drp1 subunit conformational dynamics, alters self-assembly properties, and limits cooperative GTP hydrolysis, surprisingly leading to the fission of model membranes in vitro. In vivo, the involvement of the native CT-SLiM is critical for productive mitochondrial and peroxisomal fission, as both deletion and non-native extension of the CT-SLiM severely impair their progression. Thus, contrary to prevailing models, Drp1-catalyzed membrane fission relies on allosteric communication mediated by the CT-SLiM, deceleration of GTPase activity, and coupled changes in subunit architecture and assembly-disassembly dynamics.
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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.