| Structural highlights
3uux is a 4 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | |
| Gene: | FIS1, MDV2, YIL065C (Baker's yeast), MDV1, FIS2, GAG3, NET2, YJL112W, J0802 (Baker's yeast) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[FIS1_YEAST] Has a role in mitochondrial fission. Has a role in outer membrane fission but not matrix separation. Required for targeting MDV1 to the mitochondria. Regulates the assembly of DNM1 into punctate structures, in the mitochondrial tubules, promoting mitochondrial membrane constriction and/or division.[1] [2] [3] [4] [MDV1_YEAST] Involved in mitochondrial fission. Has a partially redundant function to CAF4 in acting as an adapter protein, binding to FIS1 on the mitochondrial outer membrane and recruiting the dynamin-like GTPase DNM1 to form mitochondrial fission complexes. Formation of these complexes is required to promote constriction and fission of the mitochondrial compartment at a late step in mitochondrial division.[5] [6] [7] [8] [9] [10] [11]
Publication Abstract from PubMed
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.
Crystal structure of mitochondrial fission complex reveals scaffolding function for mitochondrial division 1 (mdv1) coiled coil.,Zhang Y, Chan NC, Ngo HB, Gristick H, Chan DC J Biol Chem. 2012 Mar 23;287(13):9855-61. Epub 2012 Feb 1. PMID:22303011[12]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mozdy AD, McCaffery JM, Shaw JM. Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. J Cell Biol. 2000 Oct 16;151(2):367-80. PMID:11038183
- ↑ Tieu Q, Nunnari J. Mdv1p is a WD repeat protein that interacts with the dynamin-related GTPase, Dnm1p, to trigger mitochondrial division. J Cell Biol. 2000 Oct 16;151(2):353-66. PMID:11038182
- ↑ Tieu Q, Okreglak V, Naylor K, Nunnari J. The WD repeat protein, Mdv1p, functions as a molecular adaptor by interacting with Dnm1p and Fis1p during mitochondrial fission. J Cell Biol. 2002 Aug 5;158(3):445-52. Epub 2002 Aug 5. PMID:12163467 doi:http://dx.doi.org/10.1083/jcb.200205031
- ↑ Jakobs S, Martini N, Schauss AC, Egner A, Westermann B, Hell SW. Spatial and temporal dynamics of budding yeast mitochondria lacking the division component Fis1p. J Cell Sci. 2003 May 15;116(Pt 10):2005-14. Epub 2003 Apr 1. PMID:12679388 doi:http://dx.doi.org/10.1242/jcs.00423
- ↑ Tieu Q, Nunnari J. Mdv1p is a WD repeat protein that interacts with the dynamin-related GTPase, Dnm1p, to trigger mitochondrial division. J Cell Biol. 2000 Oct 16;151(2):353-66. PMID:11038182
- ↑ Fekkes P, Shepard KA, Yaffe MP. Gag3p, an outer membrane protein required for fission of mitochondrial tubules. J Cell Biol. 2000 Oct 16;151(2):333-40. PMID:11038180
- ↑ Mozdy AD, McCaffery JM, Shaw JM. Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. J Cell Biol. 2000 Oct 16;151(2):367-80. PMID:11038183
- ↑ Tieu Q, Okreglak V, Naylor K, Nunnari J. The WD repeat protein, Mdv1p, functions as a molecular adaptor by interacting with Dnm1p and Fis1p during mitochondrial fission. J Cell Biol. 2002 Aug 5;158(3):445-52. Epub 2002 Aug 5. PMID:12163467 doi:http://dx.doi.org/10.1083/jcb.200205031
- ↑ Karren MA, Coonrod EM, Anderson TK, Shaw JM. The role of Fis1p-Mdv1p interactions in mitochondrial fission complex assembly. J Cell Biol. 2005 Oct 24;171(2):291-301. PMID:16247028 doi:http://dx.doi.org/10.1083/jcb.200506158
- ↑ Naylor K, Ingerman E, Okreglak V, Marino M, Hinshaw JE, Nunnari J. Mdv1 interacts with assembled dnm1 to promote mitochondrial division. J Biol Chem. 2006 Jan 27;281(4):2177-83. Epub 2005 Nov 4. PMID:16272155 doi:http://dx.doi.org/10.1074/jbc.M507943200
- ↑ Bhar D, Karren MA, Babst M, Shaw JM. Dimeric Dnm1-G385D interacts with Mdv1 on mitochondria and can be stimulated to assemble into fission complexes containing Mdv1 and Fis1. J Biol Chem. 2006 Jun 23;281(25):17312-20. Epub 2006 Apr 6. PMID:16601120 doi:http://dx.doi.org/10.1074/jbc.M513530200
- ↑ Zhang Y, Chan NC, Ngo HB, Gristick H, Chan DC. Crystal structure of mitochondrial fission complex reveals scaffolding function for mitochondrial division 1 (mdv1) coiled coil. J Biol Chem. 2012 Mar 23;287(13):9855-61. Epub 2012 Feb 1. PMID:22303011 doi:10.1074/jbc.M111.329359
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