PMID:23584531

Citation	Fröhlich, C, Grabiger, S, Schwefel, D, Faelber, K, Rosenbaum, E, Mears, J, Rocks, O and Daumke, O (2013) Structural insights into oligomerization and mitochondrial remodelling of dynamin 1-like protein. EMBO J. 32:1280-92
Abstract	Dynamin 1-like protein (DNM1L) mediates fission of mitochondria and peroxisomes, and dysfunction of DNM1L has been implicated in several neurological disorders. To study the molecular basis of mitochondrial remodelling, we determined the crystal structure of DNM1L that is comprised of a G domain, a bundle signalling element and a stalk. DNM1L assembled via a central stalk interface, and mutations in this interface disrupted dimerization and interfered with membrane binding and mitochondrial targeting. Two sequence stretches at the tip of the stalk were shown to be required for ordered assembly of DNM1L on membranes and its function in mitochondrial fission. In the crystals, DNM1L dimers further assembled via a second, previously undescribed, stalk interface to form a linear filament. Mutations in this interface interfered with liposome tubulation and mitochondrial remodelling. Based on these results and electron microscopy reconstructions, we propose an oligomerization mode for DNM1L which differs from that of dynamin and might be adapted to the remodelling of mitochondria.
Links	PubMed PMC3642683 Online version:10.1038/emboj.2013.74
Keywords	Animals; COS Cells; Cercopithecus aethiops; Crystallography, X-Ray; GTP Phosphohydrolases/antagonists & inhibitors; GTP Phosphohydrolases/chemistry; GTP Phosphohydrolases/genetics; GTP Phosphohydrolases/metabolism; Humans; Microtubule-Associated Proteins/antagonists & inhibitors; Microtubule-Associated Proteins/chemistry; Microtubule-Associated Proteins/genetics; Microtubule-Associated Proteins/metabolism; Mitochondria/drug effects; Mitochondria/genetics; Mitochondria/metabolism; Mitochondria/physiology; Mitochondrial Proteins/antagonists & inhibitors; Mitochondrial Proteins/chemistry; Mitochondrial Proteins/genetics; Mitochondrial Proteins/metabolism; Mitochondrial Size/drug effects; Mitochondrial Size/genetics; Models, Biological; Models, Molecular; Mutation, Missense/physiology; Protein Folding; Protein Multimerization/physiology; Protein Structure, Quaternary/physiology; Protein Structure, Secondary; RNA, Small Interfering/pharmacology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:DNM1L	enables	GO:0042802: identical protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:O00429-3	F		Seeded From UniProt	complete

References

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