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Crystal Structure of Mitochondrial Fission Complex Reveals Scaffolding Function for Mitochondrial Division 1 (Mdv1) Coiled Coil

Zhang, Yan and Chan, Nickie C. and Ngo, Huu B. and Gristick, Harry and Chan, David C. (2012) Crystal Structure of Mitochondrial Fission Complex Reveals Scaffolding Function for Mitochondrial Division 1 (Mdv1) Coiled Coil. Journal of Biological Chemistry, 287 (13). pp. 9855-9861. ISSN 0021-9258. PMCID PMC3323041. doi:10.1074/jbc.M111.329359. https://resolver.caltech.edu/CaltechAUTHORS:20120501-070603033

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Abstract

The mitochondrial fission machinery is best understood in the yeast Saccharomyces cerevisiae, where Fis1, Mdv1, and Dnm1 are essential components. Fis1 is a mitochondrial outer membrane protein that recruits the dynamin-related GTPase Dnm1 during the fission process. This recruitment occurs via Mdv1, which binds both Fis1 and Dnm1 and therefore functions as a molecular adaptor linking the two molecules. Mdv1 has a modular structure, consisting of an N-terminal extension that binds Fis1, a central coiled coil for dimerization, and a C-terminal WD40 repeat region that binds Dnm1. We have solved the crystal structure of a dimeric Mdv1-Fis1 complex that contains both the N-terminal extension and coiled-coil regions of Mdv1. Consistent with previous studies, Mdv1 binds Fis1 through a U-shaped helix-loop-helix motif, and dimerization of the Mdv1-Fis1 complex is mediated by the antiparallel coiled coil of Mdv1. However, the complex is surprisingly compact and rigid due to two additional contacts mediated by the surface of the Mdv1 coiled coil. The coiled coil packs against both Fis1 and the second helix of the Mdv1 helix-loop-helix motif. Mutational analyses showed that these contacts are important for mitochondrial fission activity. These results indicate that, in addition to dimerization, the unusually long Mdv1 coiled coil serves a scaffolding function to stabilize the Mdv1-Fis1 complex.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1074/jbc.M111.329359DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323041/PubMed CentralArticle
ORCID:
AuthorORCID
Gristick, Harry0000-0002-1957-2821
Chan, David C.0000-0002-0191-2154
Additional Information:© 2012 by The American Society for Biochemistry and Molecular Biology, Inc. This work was supported, in whole or in part, by National Institutes of Health Grants GM083121 and GM062967. The atomic coordinates and structure factors (code 3UUX) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/). Supported in part by a postdoctoral fellowship from the American Heart Association. We thank Janet Shaw for yeast strains, constructs, and helpful discussions. Some of the initial screening was done at the Molecular Observatory at California Institute of Technology, which is supported by the Gordon and Betty Moore Foundation and the Sanofi-Aventis Bioengineering Research Program. Portions of this work were carried out at the Stanford Synchrotron Radiation Lightsource, a Directorate of the SLAC National Accelerator Laboratory and an Office of Science User Facility operated for the United States Department of Energy Office of Science by Stanford University. The Stanford Synchrotron Radiation Lightsource Structural Molecular Biology Program is supported by the Department of Energy Office of Biological and Environmental Research and by National Institutes of Health National Center for Research Resources Biomedical Technology Program Grant P41RR001209 and NIGMS.
Funders:
Funding AgencyGrant Number
NIHGM083121
NIHGM062967
American Heart AssociationUNSPECIFIED
Gordon and Betty Moore FoundationUNSPECIFIED
Sanofi-Aventis Bioengineering Research ProgramUNSPECIFIED
Department of Energy (DOE)UNSPECIFIED
NIHP41RR001209
National Institute of General Medical SciencesUNSPECIFIED
Issue or Number:13
PubMed Central ID:PMC3323041
DOI:10.1074/jbc.M111.329359
Record Number:CaltechAUTHORS:20120501-070603033
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20120501-070603033
Official Citation:Crystal Structure of Mitochondrial Fission Complex Reveals Scaffolding Function for Mitochondrial Division 1 (Mdv1) Coiled Coil Yan Zhang, Nickie C. Chan, Huu B. Ngo, Harry Gristick, and David C. Chan J. Biol. Chem. 2012 287: 9855-9861. First Published on February 1, 2012, doi:10.1074/jbc.M111.329359
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:30404
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:01 May 2012 14:43
Last Modified:09 Nov 2021 19:47

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