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PDBsum entry 2pqr

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protein metals Protein-protein interface(s) links
Apoptosis PDB id
2pqr
Jmol
Contents
Protein chains
98 a.a. *
124 a.a. *
40 a.a. *
45 a.a. *
Metals
_AU ×2
Waters ×141
* Residue conservation analysis
PDB id:
2pqr
Name: Apoptosis
Title: Crystal structure of yeast fis1 complexed with a fragment of caf4
Structure: Mitochondria fission 1 protein. Chain: a, b. Fragment: cytoplasmic portion. Synonym: mitochondrial division protein 2. Engineered: yes. Wd repeat protein ykr036c. Chain: c, d. Fragment: n-terminal domain. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: fis1, mdv2. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: caf4.
Resolution:
1.88Å     R-factor:   0.209     R-free:   0.241
Authors: Y.Zhang,D.C.Chan
Key ref:
Y.Zhang and D.C.Chan (2007). Structural basis for recruitment of mitochondrial fission complexes by Fis1. Proc Natl Acad Sci U S A, 104, 18526-18530. PubMed id: 17998537 DOI: 10.1073/pnas.0706441104
Date:
02-May-07     Release date:   06-Nov-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P40515  (FIS1_YEAST) -  Mitochondria fission 1 protein
Seq:
Struc:
155 a.a.
98 a.a.
Protein chain
Pfam   ArchSchema ?
P40515  (FIS1_YEAST) -  Mitochondria fission 1 protein
Seq:
Struc:
155 a.a.
124 a.a.
Protein chain
Pfam   ArchSchema ?
P36130  (CAF4_YEAST) -  CCR4-associated factor 4
Seq:
Struc:
 
Seq:
Struc:
643 a.a.
40 a.a.
Protein chain
Pfam   ArchSchema ?
P36130  (CAF4_YEAST) -  CCR4-associated factor 4
Seq:
Struc:
 
Seq:
Struc:
643 a.a.
45 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     mitochondrial fission   1 term 

 

 
DOI no: 10.1073/pnas.0706441104 Proc Natl Acad Sci U S A 104:18526-18530 (2007)
PubMed id: 17998537  
 
 
Structural basis for recruitment of mitochondrial fission complexes by Fis1.
Y.Zhang, D.C.Chan.
 
  ABSTRACT  
 
Mitochondrial fission controls mitochondrial shape and physiology, including mitochondrial remodeling in apoptosis. During assembly of the yeast mitochondrial fission complex, the outer membrane protein Fis1 recruits the dynamin-related GTPase Dnm1 to mitochondria. Fis1 contains a tetratricopeptide repeat (TPR) domain and interacts with Dnm1 via the molecular adaptors Mdv1 and Caf4. By using crystallographic analysis of adaptor-Fis1 complexes, we show that these adaptors use two helices to bind to both the concave and convex surfaces of the Fis1 TPR domain. Fis1 therefore contains two interaction interfaces, a binding mode that, to our knowledge, has not been observed previously for TPR domains. Genetic and biochemical studies indicate that both binding interfaces are important for binding of Mdv1 and Caf4 to Fis1 and for mitochondrial fission activity in vivo. Our results reveal how Fis1 recruits the mitochondrial fission complex and will facilitate efforts to manipulate mitochondrial fission.
 
  Selected figure(s)  
 
Figure 1.
Structures of Fis1/Mdv1 and Fis1/Caf4 complexes. (A) Domain arrangement of Mdv1, Caf4, and Fis1. Regions A and B in Caf4, located in the N-terminal extension, directly bind Fis1, as shown in the crystal structure (C). The corresponding region B and the predicted region A in Mdv1 are also labeled. For each protein, the region within the blue frame is present in the crystallization studies. (B) Crystal structure of the Fis1/Mdv1 complex depicted in a ribbon representation. The Fis1 N-terminal arm (red) remains packed against the original hydrophobic groove and stabilizes the αB helix of Mdv1 (cyan), which packs against a second hydrophobic groove on the concave surface of Fis1. (C) Crystal structure of the Fis1/Caf4 complex. In addition to the αB helix packed against the concave Fis1 surface, Caf4 (purple) uses the αA helix and the intervening loop to bind the convex Fis1 surface. (D) The Fis1/Caf4 structure with Fis1 shown in a surface representation. The long loop allows Caf4 to straddle both sides of the Fis1 TPR domain.
Figure 4.
Surface residues essential for Fis1 function. (A) Immunoprecipitation of HA-tagged Mdv1 by Myc-tagged Fis1 containing mutations in surface residues contacting the αB helix of adaptors. wt, wild type. (B) Ability of Fis1 mutants to rescue mitochondrial morphology and Dnm1 recruitment in fis1Δ yeast. Mitochondrial morphology was scored by using mito-DsRed. Subcellular localization of GFP–Dnm1 puncta was scored by comparison with mito-DsRed. (C) Schematic of fission complex recruitment by Fis1. In the unliganded state (shown at left), Fis1 resides in the mitochondrial outer membrane (OM) with its N-terminal arm (red region) packed against the concave surface of the TPR domain. The adaptors Mdv1 and Caf4 use two N-terminal helices to bind Fis1. The Fis1 N-terminal arm stabilizes adaptor binding by interacting with the αB helix (complex shown at right). The WD40 region of the adaptors then recruits Dnm1 to the mitochondria. Dnm1 exists as dimers and is activated by assembly into higher-order oligomers (not shown).
 
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23334420 Y.M.Abbas, A.Pichlmair, M.W.Górna, G.Superti-Furga, and B.Nagar (2013).
Structural basis for viral 5'-PPP-RNA recognition by human IFIT proteins.
  Nature, 494, 60-64.
PDB codes: 4hoq 4hor 4hos 4hot 4hou
20601194 G.J.Tranah (2011).
Mitochondrial-nuclear epistasis: implications for human aging and longevity.
  Ageing Res Rev, 10, 238-252.  
21170049 J.A.Mears, L.L.Lackner, S.Fang, E.Ingerman, J.Nunnari, and J.E.Hinshaw (2011).
Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission.
  Nat Struct Mol Biol, 18, 20-26.  
21277336 T.Landes, and J.C.Martinou (2011).
Mitochondrial outer membrane permeabilization during apoptosis: the role of mitochondrial fission.
  Biochim Biophys Acta, 1813, 540-545.  
20726898 A.Bink, G.Govaert, I.E.François, K.Pellens, L.Meerpoel, M.Borgers, G.Van Minnebruggen, V.Vroome, B.P.Cammue, and K.Thevissen (2010).
A fungicidal piperazine-1-carboxamidine induces mitochondrial fission-dependent apoptosis in yeast.
  FEMS Yeast Res, 10, 812-818.  
21102612 B.Westermann (2010).
Mitochondrial fusion and fission in cell life and death.
  Nat Rev Mol Cell Biol, 11, 872-884.  
21109195 C.Zechner, L.Lai, J.F.Zechner, T.Geng, Z.Yan, J.W.Rumsey, D.Collia, Z.Chen, D.F.Wozniak, T.C.Leone, and D.P.Kelly (2010).
Total skeletal muscle PGC-1 deficiency uncouples mitochondrial derangements from fiber type determination and insulin sensitivity.
  Cell Metab, 12, 633-642.  
21149567 H.Otera, C.Wang, M.M.Cleland, K.Setoguchi, S.Yokota, R.J.Youle, and K.Mihara (2010).
Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells.
  J Cell Biol, 191, 1141-1158.  
19864424 M.N.Serasinghe, A.M.Seneviratne, A.V.Smrcka, and Y.Yoon (2010).
Identification and characterization of unique proline-rich peptides binding to the mitochondrial fission protein hFis1.
  J Biol Chem, 285, 620-630.  
21149566 S.Koirala, H.T.Bui, H.L.Schubert, D.M.Eckert, C.P.Hill, M.S.Kay, and J.M.Shaw (2010).
Molecular architecture of a dynamin adaptor: implications for assembly of mitochondrial fission complexes.
  J Cell Biol, 191, 1127-1139.
PDB code: 2xu6
19696024 E.R.Rafikova, K.Melikov, C.Ramos, L.Dye, and L.V.Chernomordik (2009).
Transmembrane protein-free membranes fuse into xenopus nuclear envelope and promote assembly of functional pores.
  J Biol Chem, 284, 29847-29859.  
19476438 H.Kitagaki (2009).
Mitochondrial-morphology-targeted breeding of industrial yeast strains for alcohol fermentation.
  Biotechnol Appl Biochem, 53, 145-153.  
19759282 J.A.Heymann, and J.E.Hinshaw (2009).
Dynamins at a glance.
  J Cell Sci, 122, 3427-3431.  
19522466 L.K.Picton, S.Casares, A.C.Monahan, A.Majumdar, and R.B.Hill (2009).
Evidence for conformational heterogeneity of fission protein Fis1 from Saccharomyces cerevisiae.
  Biochemistry, 48, 6598-6609.  
19225618 S.Balaji, L.M.Iyer, and L.Aravind (2009).
HPC2 and ubinuclein define a novel family of histone chaperones conserved throughout eukaryotes.
  Mol Biosyst, 5, 269-275.  
19076450 A.B.Knott, and E.Bossy-Wetzel (2008).
Impairing the mitochondrial fission and fusion balance: a new mechanism of neurodegeneration.
  Ann N Y Acad Sci, 1147, 283-292.  
18568013 A.B.Knott, G.Perkins, R.Schwarzenbacher, and E.Bossy-Wetzel (2008).
Mitochondrial fragmentation in neurodegeneration.
  Nat Rev Neurosci, 9, 505-518.  
18776008 J.Koo, S.Tammam, S.Y.Ku, L.M.Sampaleanu, L.L.Burrows, and P.L.Howell (2008).
PilF is an outer membrane lipoprotein required for multimerization and localization of the Pseudomonas aeruginosa Type IV pilus secretin.
  J Bacteriol, 190, 6961-6969.
PDB code: 2ho1
18845145 M.N.Serasinghe, and Y.Yoon (2008).
The mitochondrial outer membrane protein hFis1 regulates mitochondrial morphology and fission through self-interaction.
  Exp Cell Res, 314, 3494-3507.  
18353969 S.Gandre-Babbe, and A.M.van der Bliek (2008).
The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells.
  Mol Biol Cell, 19, 2402-2412.  
18513378 S.Nagotu, A.M.Krikken, M.Otzen, J.A.Kiel, M.Veenhuis, and I.J.van der Klei (2008).
Peroxisome fission in Hansenula polymorpha requires Mdv1 and Fis1, two proteins also involved in mitochondrial fission.
  Traffic, 9, 1471-1484.  
18477482 W.C.Cheng, K.M.Leach, and J.M.Hardwick (2008).
Mitochondrial death pathways in yeast and mammalian cells.
  Biochim Biophys Acta, 1783, 1272-1279.  
18756280 W.C.Cheng, X.Teng, H.K.Park, C.M.Tucker, M.J.Dunham, and J.M.Hardwick (2008).
Fis1 deficiency selects for compensatory mutations responsible for cell death and growth control defects.
  Cell Death Differ, 15, 1838-1846.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.