Structural basis of mitochondrial receptor binding and constriction by DRP1.
In: Nature, Jg. 558 (2018-06-21), Heft 7710, S. 401-405
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Zugriff:
Mitochondrial inheritance, genome maintenance and metabolic adaptation depend on organelle fission by dynamin-related protein 1 (DRP1) and its mitochondrial receptors. DRP1 receptors include the paralogues mitochondrial dynamics proteins of 49 and 51 kDa (MID49 and MID51) and mitochondrial fission factor (MFF); however, the mechanisms by which these proteins recruit and regulate DRP1 are unknown. Here we present a cryo-electron microscopy structure of full-length human DRP1 co-assembled with MID49 and an analysis of structure- and disease-based mutations. We report that GTP induces a marked elongation and rotation of the GTPase domain, bundle-signalling element and connecting hinge loops of DRP1. In this conformation, a network of multivalent interactions promotes the polymerization of a linear DRP1 filament with MID49 or MID51. After co-assembly, GTP hydrolysis and exchange lead to MID receptor dissociation, filament shortening and curling of DRP1 oligomers into constricted and closed rings. Together, these views of full-length, receptor- and nucleotide-bound conformations reveal how DRP1 performs mechanical work through nucleotide-driven allostery. Cryo-electron microscopy is used to resolve the structure of human dynamin-related protein 1 co-assembled with its receptor mitochondrial dynamics protein of 49 kDa, along with an analysis of structure- and disease-based mutations. [ABSTRACT FROM AUTHOR]
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Titel: |
Structural basis of mitochondrial receptor binding and constriction by DRP1.
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Autor/in / Beteiligte Person: | Kalia, Raghav ; Wang, Ray Yu-Ruei ; Yusuf, Ali ; Thomas, Paul V. ; Agard, David A. ; Shaw, Janet M. ; Frost, Adam |
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Zeitschrift: | Nature, Jg. 558 (2018-06-21), Heft 7710, S. 401-405 |
Veröffentlichung: | 2018 |
Medientyp: | academicJournal |
ISSN: | 0028-0836 (print) |
DOI: | 10.1038/s41586-018-0211-2 |
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