Structure of a mitochondrial fission dynamin in the closed conformation

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Title: Structure of a mitochondrial fission dynamin in the closed conformation
Authors: Bohuszewicz, O
Low, HH
Item Type: Journal Article
Abstract: Dynamin 1-like proteins (DNM1-L) are mechanochemical GTPases that induce membrane fission in mitochondria and peroxisomes. Their mechanism depends on conformational changes driven by nucleotide and lipid cycling. Here we show the crystal structure of a mitochondrial fission dynamin (CmDnm1) from the algae Cyanidioschyzon merolae. Unlike other eukaryotic dynamin structures, CmDnm1 is in a hinge 1 closed conformation, with the GTPase domain compacted against the stalk. Within the crystal, CmDnm1 packs as a diamond-shaped tetramer that is consistent with an inactive off-membrane state. Crosslinking, photoinduced electron transfer assays, and electron microscopy verify these structures. In vitro, CmDnm1 forms concentration-dependent rings and protein–lipid tubes reminiscent of DNM1-L and classical dynamin with hinge 1 open. Our data provides a mechanism for filament collapse and membrane release that may extend to other dynamin family members. Additionally, hinge 1 closing may represent a key conformational change that contributes to membrane fission.
Issue Date: 1-Aug-2018
Date of Acceptance: 26-Jun-2018
URI: http://hdl.handle.net/10044/1/62207
DOI: https://dx.doi.org/10.1038/s41594-018-0097-6
ISSN: 1545-9985
Publisher: Nature Publishing Group
Start Page: 722
End Page: 731
Journal / Book Title: Nature Structural and Molecular Biology
Volume: 25
Issue: 8
Copyright Statement: © 2018 Springer-Nature. The final publication is available at Springer via https://dx.doi.org/10.1038/s41594-018-0097-6
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 097328/Z/11/ZR
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biophysics
Cell Biology
CRYSTAL-STRUCTURE
MEMBRANE FISSION
PEROXISOMAL FISSION
MAMMALIAN-CELLS
STALK REGION
PROTEIN
DOMAIN
GTPASE
CONSTRICTION
DIMERIZATION
11 Medical And Health Sciences
03 Chemical Sciences
06 Biological Sciences
Biophysics
Developmental Biology
Publication Status: Published
Online Publication Date: 2018-07-30
Appears in Collections:Faculty of Natural Sciences



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