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Structural insights into oligomerization and mitochondrial remodelling of dynamin 1-like protein.
- Source :
-
The EMBO journal [EMBO J] 2013 May 02; Vol. 32 (9), pp. 1280-92. Date of Electronic Publication: 2013 Apr 12. - Publication Year :
- 2013
-
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.
- Subjects :
- Animals
COS Cells
Chlorocebus aethiops
Crystallography, X-Ray
Dynamins
GTP Phosphohydrolases antagonists & inhibitors
GTP Phosphohydrolases genetics
Humans
Microtubule-Associated Proteins antagonists & inhibitors
Microtubule-Associated Proteins genetics
Mitochondria drug effects
Mitochondria genetics
Mitochondrial Proteins antagonists & inhibitors
Mitochondrial Proteins genetics
Mitochondrial Size drug effects
Mitochondrial Size genetics
Models, Biological
Models, Molecular
Mutation, Missense physiology
Protein Folding
Protein Structure, Quaternary physiology
Protein Structure, Secondary
RNA, Small Interfering pharmacology
GTP Phosphohydrolases chemistry
GTP Phosphohydrolases metabolism
Microtubule-Associated Proteins chemistry
Microtubule-Associated Proteins metabolism
Mitochondria metabolism
Mitochondria physiology
Mitochondrial Proteins chemistry
Mitochondrial Proteins metabolism
Protein Multimerization physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2075
- Volume :
- 32
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 23584531
- Full Text :
- https://doi.org/10.1038/emboj.2013.74