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Structural Basis for Regulated Assembly of the Mitochondrial Fission GTPase Drp1
Open accessPreprint — published as 10.1038/s41467-024-45524-4 · Paper page
Abstract
Mitochondrial fission is crucial for distributing cellular energy throughout cells and for isolating damaged regions of the organelle that are targeted for degradation. This multistep process is initiated by the enhanced recruitment and oligomerization of dynamin-related protein 1 (Drp1) at the surface of mitochondria. As such, Drp1 is essential for inducing mitochondrial division in mammalian cells, and homologous proteins are found in all eukaryotes. De novo missense mutations in the Drp1 gene, DNM1L, are associated with severe neurodevelopmental diseases in patients, and no effective treatments are available. As a member of the dynamin superfamily of proteins (DSPs), controlled Drp1 self-assembly into large helical polymers stimulates its GTPase activity to promote membrane constriction. Still, little is known about the regulatory mechanisms that determine when and where Drp1 self-assembles, and proper mitochondrial dynamics requires correct spatial and temporal assembly of the fission machinery. Here we present a cryo-EM structure of a full-length, native Drp1 dimer in an auto-inhibited state. This dimer reveals two key conformational rearrangements that must be unlocked through intermolecular interactions to achieve the assembly competent state previously observed in crystal and filament structures. Specifically, the G domain is closed against the stalk domain and occludes intermolecular interactions necessary for self-assembly beyond a dimer. Similarly, adjacent stalks in the dimer form a more continuous interface that further occludes conserved intermolecular contact sites. This structural insight provides a novel mechanism for regulated self-assembly of the mitochondrial fission machinery.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
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Research works printed but not linked: 34
- 10.1016/0092-8674(94)90190-2 · DOI
- 10.1016/j.tcb.2018.11.003 · DOI
- Francy, C. A. , Clinton, R. W. , Frohlich, C. , Murphy, C. & Mears, J. A . Cryo-EM Studies of Drp1 Reveal Cardiolipin Interactions that Activate the Helical Oligomer. Scientific reports 7, 3 (2017). https://doi.org:10.1038/s41598-017-11008-3 [doi] · DOI
- 10.1038/s41586-018-0211-2 · DOI
- 10.1093/emboj/20.21.5813 · DOI
- 10.1038/nature08972 · DOI
- 10.1073/pnas.0506491102 · DOI
- 10.1038/nature10441 · DOI
- 10.1038/emboj.2013.74 · DOI
- 10.1038/nature10369 · DOI · Paper page
- 10.1016/j.immuni.2011.07.012 · DOI
- 10.1016/j.cell.2011.09.003 · DOI
- Mahajan, M. et al. NMR identification of a conserved Drp1 cardiolipin-binding motif essential for stress-induced mitochondrial fission. Proc Natl Acad Sci U S A 118 (2021). https://doi.org:10.1073/pnas.2023079118 · DOI
- 10.1074/jbc.M112.342105 · DOI
- 10.1091/mbc.E14-02-0728 · DOI
- 10.1074/jbc.M110.142430 · DOI
- 10.1083/jcb.200506078 · DOI
- 2018, Structure of a mitochondrial fission dynamin in the closed conformation, Nat Struct Mol Biol, 25, 722, 10.1038/s41594-018-0097-6 · DOI
- 10.1074/jbc.M115.680025 · DOI
- 10.1007/978-1-0716-0676-6_4 · DOI
- 10.1038/nmeth.4169 · DOI · Paper page
- 10.1038/nmeth.4193 · DOI
- 2019, Positive-unlabeled convolutional neural networks for particle picking in cryo-electron micrographs, Nat Methods, 16, 1153, 10.1038/s41592-019-0575-8 · DOI
- 10.1038/s41592-020-00990-8 · DOI
- 10.1002/jcc.20084 · DOI
- 10.1093/NAR/GKAB1061 · DOI · Paper page
- 10.1016/0263-7855(96)00018-5 · DOI · Paper page
- 10.1016/j.str.2008.03.005 · DOI
- 10.1107/S2059798319011471 · DOI · Paper page
- 10.1107/S2059798318006551 · DOI
- 10.1074/jbc.M114.610881 · DOI
- 10.1016/S0091-679X(08)00413-5 · DOI
- 10.1083/jcb.200903065 · DOI · Paper page
- Bora, P. et al. p38-MAPK-mediated translation regulation during early blastocyst development is required for primitive endoderm differentiation in mice. Commun Biol 4, 788 (2021). https://doi.org:10.1038/s42003-021-02290-z · DOI
Metadata
- Authors
- Rochon, K., Bauer, B. L., Roethler, N. A., Buckley, Y., Su, C.-C., Huang, W., Ramachandran, R., Stoll, M. S. K., Yu, E. W., Taylor, D. J., & Mears, J. A.
- Affiliations
- Case Western Reserve University (US)
- Corresponding author
- Mears, Jason A.
- ORCID
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2023-06-22
- Volume
- 15
- Issue
- 1
- Pages
- 1328-1328
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10864337
- OpenAlex
- W4391786421
- Cited by
- 52
- References
- 1
- Citations by year
- 2026: 24 · 2025: 22 · 2024: 5 · 2023: 1
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health and Human Services (R01 GM125844, U24GM116792, F31 GM139324)
- Case Western Reserve University
- National Institutes of Health (1s10od016164-01, AI145069, GM125844)
- University of California, Los Angeles
- University of California, San Francisco
- National Institute of General Medical Sciences (R01GM121583, P41 RR-01081, F31GM139324, T32GM008803, U24GM116792, GM125844, R01GM125844)
- National Institute of Allergy and Infectious Diseases (R01AI145069)
- National Center for Research Resources (P41RR001081)
- Office of Research Infrastructure Programs, National Institutes of Health (S10 OD016164)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- Drp1, mitochondrial fission, dynamin-related proteins, dynamin superfamily, GTPase activity, protein self-assembly, conformational change, mitochondrial division, membrane constriction
- MeSH terms
- Animals, Mammals, Microtubule-Associated Proteins, Mitochondria, GTP Phosphohydrolases, Mitochondrial Proteins, Dynamins, Mitochondrial Dynamics
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