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Transferase PDB id
1dvp
Jmol
Contents
Protein chain
217 a.a. *
Ligands
CIT
Metals
_ZN ×2
Waters ×237
* Residue conservation analysis
PDB id:
1dvp
Name: Transferase
Title: Crystal structure of the vhs and fyve tandem domains of hrs, a protein involved in membrane trafficking and signal transduction
Structure: Hepatocyte growth factor-regulated tyrosine kinase substrate. Chain: a. Fragment: n-terminal vhs and fyve tandem domains. Synonym: hrs. Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
Resolution:
2.00Å     R-factor:   0.215     R-free:   0.254
Authors: Y.Mao,A.Nickitenko,X.Duan,T.E.Lloyd,M.N.Wu,H.Bellen, F.A.Quiocho
Key ref:
Y.Mao et al. (2000). Crystal structure of the VHS and FYVE tandem domains of Hrs, a protein involved in membrane trafficking and signal transduction. Cell, 100, 447-456. PubMed id: 10693761 DOI: 10.1016/S0092-8674(00)80680-7
Date:
21-Jan-00     Release date:   06-Mar-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q960X8  (HRS_DROME) -  Hepatocyte growth factor-regulated tyrosine kinase substrate
Seq:
Struc: 		 
Seq:
Struc: 		760 a.a.
217 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     intracellular protein transport   1 term 
  Biochemical function     zinc ion binding     1 term  

 

 
DOI no: 10.1016/S0092-8674(00)80680-7 Cell 100:447-456 (2000)
PubMed id: 10693761  
 
 
Crystal structure of the VHS and FYVE tandem domains of Hrs, a protein involved in membrane trafficking and signal transduction.
Y.Mao, A.Nickitenko, X.Duan, T.E.Lloyd, M.N.Wu, H.Bellen, F.A.Quiocho.
 
  ABSTRACT  
 
We have determined the 2 A X-ray structure of the 219-residue N-terminal VHS and FYVE tandem domain unit of Drosophila Hrs. The unit assumes a pyramidal structure in which the much larger VHS domain (residues 1-153) forms a rectangular base and the FYVE domain occupies the apical end. The VHS domain is comprised of an unusual "superhelix" of eight alpha helices, and the FYVE domain is mainly built of loops, two double-stranded antiparallel sheets, and a helix stabilized by two tetrahedrally coordinated zinc atoms. The two-domain structure forms an exact 2-fold-related homodimer through antiparallel association of mainly FYVE domains. Dimerization creates two identical pockets designed for binding ligands with multiple negative charges such as citrate or phosphatidylinositol 3-phosphate.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. Electrostatic Surface Potential (±10 kT) of the Homodimer of the VHS-FYVE Tandem Domains 		Figure 6.
Figure 6. Model of the Interaction of the VHS and FYVE Tandem Domains with the Membrane
 
  The above figures are reprinted by permission from Cell Press: Cell (2000, 100, 447-456) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20678208 E.Wywial, and S.M.Singh (2010).
Identification and structural characterization of FYVE domain-containing proteins of Arabidopsis thaliana.
  BMC Plant Biol, 10, 157.  
20559318 T.G.Kutateladze (2010).
Translation of the phosphoinositide code by PI effectors.
  Nat Chem Biol, 6, 507-513.  
20150893 X.Ren, and J.H.Hurley (2010).
VHS domains of ESCRT-0 cooperate in high-avidity binding to polyubiquitinated cargo.
  EMBO J, 29, 1045-1054.
PDB code: 3ldz
20026658 C.S.Wood, K.R.Schmitz, N.J.Bessman, T.G.Setty, K.M.Ferguson, and C.G.Burd (2009).
PtdIns4P recognition by Vps74/GOLPH3 links PtdIns 4-kinase signaling to retrograde Golgi trafficking.
  J Cell Biol, 187, 967-975.
PDB code: 3kn1
19282972 G.A.Palidwor, S.Shcherbinin, M.R.Huska, T.Rasko, U.Stelzl, A.Arumughan, R.Foulle, P.Porras, L.Sanchez-Pulido, E.E.Wanker, and M.A.Andrade-Navarro (2009).
Detection of alpha-rod protein repeats using a neural network and application to huntingtin.
  PLoS Comput Biol, 5, e1000304.  
  20054405 L.V.Omelyanchuk, J.A.Pertseva, S.S.Burns, and L.S.Chang (2009).
Evolution and Origin of HRS, a Protein Interacting with Merlin, the Neurofibromatosis 2 Gene Product.
  Gene Regul Syst Bio, 3, 143-157.  
19278655 X.Ren, D.P.Kloer, Y.C.Kim, R.Ghirlando, L.F.Saidi, G.Hummer, and J.H.Hurley (2009).
Hybrid structural model of the complete human ESCRT-0 complex.
  Structure, 17, 406-416.
PDB code: 3f1i
17065551 C.Commisso, and G.L.Boulianne (2007).
The NHR1 domain of Neuralized binds Delta and mediates Delta trafficking and Notch signaling.
  Mol Biol Cell, 18, 1.  
17543868 G.Prag, H.Watson, Y.C.Kim, B.M.Beach, R.Ghirlando, G.Hummer, J.S.Bonifacino, and J.H.Hurley (2007).
The Vps27/Hse1 complex is a GAT domain-based scaffold for ubiquitin-dependent sorting.
  Dev Cell, 12, 973-986.
PDB code: 2pjw
17905827 H.D.Mertens, J.M.Callaghan, J.D.Swarbrick, M.J.McConville, and P.R.Gooley (2007).
A high-resolution solution structure of a trypanosomatid FYVE domain.
  Protein Sci, 16, 2552-2559.
PDB code: 1z2q
17289673 M.T.McIntosh, A.Vaid, H.D.Hosgood, J.Vijay, A.Bhattacharya, M.H.Sahani, P.Baevova, K.A.Joiner, and P.Sharma (2007).
Traffic to the malaria parasite food vacuole: a novel pathway involving a phosphatidylinositol 3-phosphate-binding protein.
  J Biol Chem, 282, 11499-11508.  
17450176 R.L.Williams, and S.Urbé (2007).
The emerging shape of the ESCRT machinery.
  Nat Rev Mol Cell Biol, 8, 355-368.  
17707914 T.G.Kutateladze (2007).
Mechanistic similarities in docking of the FYVE and PX domains to phosphatidylinositol 3-phosphate containing membranes.
  Prog Lipid Res, 46, 315-327.  
16470805 C.H.Lu, Y.S.Lin, Y.C.Chen, C.S.Yu, S.Y.Chang, and J.K.Hwang (2006).
The fragment transformation method to detect the protein structural motifs.
  Proteins, 63, 636-643.  
16689637 J.H.Hurley, and S.D.Emr (2006).
The ESCRT complexes: structure and mechanism of a membrane-trafficking network.
  Annu Rev Biophys Biomol Struct, 35, 277-298.  
16644267 T.G.Kutateladze (2006).
Phosphatidylinositol 3-phosphate recognition and membrane docking by the FYVE domain.
  Biochim Biophys Acta, 1761, 868-877.  
15866031 L.Nguyen, and J.Pieters (2005).
The Trojan horse: survival tactics of pathogenic mycobacteria in macrophages.
  Trends Cell Biol, 15, 269-276.  
16331966 R.Brunecky, S.Lee, P.W.Rzepecki, M.Overduin, G.D.Prestwich, A.G.Kutateladze, and T.G.Kutateladze (2005).
Investigation of the binding geometry of a peripheral membrane protein.
  Biochemistry, 44, 16064-16071.  
16141328 S.A.Lee, R.Eyeson, M.L.Cheever, J.Geng, V.V.Verkhusha, C.Burd, M.Overduin, and T.G.Kutateladze (2005).
Targeting of the FYVE domain to endosomal membranes is regulated by a histidine switch.
  Proc Natl Acad Sci U S A, 102, 13052-13057.  
15590643 S.C.Lee, H.H.Guan, C.H.Wang, W.N.Huang, S.C.Tjong, C.J.Chen, and W.G.Wu (2005).
Structural basis of citrate-dependent and heparan sulfate-mediated cell surface retention of cobra cardiotoxin A3.
  J Biol Chem, 280, 9567-9577.
PDB code: 1xt3
15869386 W.Cho, and R.V.Stahelin (2005).
Membrane-protein interactions in cell signaling and membrane trafficking.
  Annu Rev Biophys Biomol Struct, 34, 119-151.  
14594806 A.Hayakawa, S.J.Hayes, D.C.Lawe, E.Sudharshan, R.Tuft, K.Fogarty, D.Lambright, and S.Corvera (2004).
Structural basis for endosomal targeting by FYVE domains.
  J Biol Chem, 279, 5958-5966.  
15496406 C.Gorbea, G.M.Goellner, K.Teter, R.K.Holmes, and M.Rechsteiner (2004).
Characterization of mammalian Ecm29, a 26 S proteasome-associated protein that localizes to the nucleus and membrane vesicles.
  J Biol Chem, 279, 54849-54861.  
15473838 D.J.Owen, B.M.Collins, and P.R.Evans (2004).
Adaptors for clathrin coats: structure and function.
  Annu Rev Cell Dev Biol, 20, 153-191.  
14708007 J.S.Bonifacino (2004).
The GGA proteins: adaptors on the move.
  Nat Rev Mol Cell Biol, 5, 23-32.  
15170460 M.A.De Matteis, and A.Godi (2004).
PI-loting membrane traffic.
  Nat Cell Biol, 6, 487-492.  
15576038 M.D.Tibbetts, E.N.Shiozaki, L.Gu, E.R.McDonald, W.S.El-Deiry, and Y.Shi (2004).
Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2.
  Structure, 12, 2257-2263.
PDB code: 1y02
15056867 M.Yamakami, and H.Yokosawa (2004).
Tom1 (target of Myb 1) is a novel negative regulator of interleukin-1- and tumor necrosis factor-induced signaling pathways.
  Biol Pharm Bull, 27, 564-566.  
15452113 N.R.Blatner, R.V.Stahelin, K.Diraviyam, P.T.Hawkins, W.Hong, D.Murray, and W.Cho (2004).
The molecular basis of the differential subcellular localization of FYVE domains.
  J Biol Chem, 279, 53818-53827.  
14578346 T.G.Kutateladze, D.G.Capelluto, C.G.Ferguson, M.L.Cheever, A.G.Kutateladze, G.D.Prestwich, and M.Overduin (2004).
Multivalent mechanism of membrane insertion by the FYVE domain.
  J Biol Chem, 279, 3050-3057.  
12972556 E.Mizuno, K.Kawahata, M.Kato, N.Kitamura, and M.Komada (2003).
STAM proteins bind ubiquitinated proteins on the early endosome via the VHS domain and ubiquitin-interacting motif.
  Mol Biol Cell, 14, 3675-3689.  
14745135 K.Nakayama, and S.Wakatsuki (2003).
The structure and function of GGAs, the traffic controllers at the TGN sorting crossroads.
  Cell Struct Funct, 28, 431-442.  
12486728 M.Albrecht, D.Hoffmann, B.O.Evert, I.Schmitt, U.Wüllner, and T.Lengauer (2003).
Structural modeling of ataxin-3 reveals distant homology to adaptins.
  Proteins, 50, 355-370.  
14563850 M.Yamakami, T.Yoshimori, and H.Yokosawa (2003).
Tom1, a VHS domain-containing protein, interacts with tollip, ubiquitin, and clathrin.
  J Biol Chem, 278, 52865-52872.  
12388763 H.Dewar, D.T.Warren, F.C.Gardiner, C.G.Gourlay, N.Satish, M.R.Richardson, P.D.Andrews, and K.R.Ayscough (2002).
Novel proteins linking the actin cytoskeleton to the endocytic machinery in Saccharomyces cerevisiae.
  Mol Biol Cell, 13, 3646-3661.  
11796224 J.H.Hurley, D.E.Anderson, B.Beach, B.Canagarajah, Y.S.Ho, E.Jones, G.Miller, S.Misra, M.Pearson, L.Saidi, S.Suer, R.Trievel, and Y.Tsujishita (2002).
Structural genomics and signaling domains.
  Trends Biochem Sci, 27, 48-53.  
11733501 J.Kunz, A.Fuelling, L.Kolbe, and R.A.Anderson (2002).
Stereo-specific substrate recognition by phosphatidylinositol phosphate kinases is swapped by changing a single amino acid residue.
  J Biol Chem, 277, 5611-5619.  
12058068 M.Geyer, O.T.Fackler, and B.M.Peterlin (2002).
Subunit H of the V-ATPase involved in endocytosis shows homology to beta-adaptins.
  Mol Biol Cell, 13, 2045-2056.  
12006563 R.V.Stahelin, F.Long, K.Diraviyam, K.S.Bruzik, D.Murray, and W.Cho (2002).
Phosphatidylinositol 3-phosphate induces the membrane penetration of the FYVE domains of Vps27p and Hrs.
  J Biol Chem, 277, 26379-26388.  
11832215 T.E.Lloyd, R.Atkinson, M.N.Wu, Y.Zhou, G.Pennetta, and H.J.Bellen (2002).
Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila.
  Cell, 108, 261-269.  
11395417 B.Vanhaesebroeck, S.J.Leevers, K.Ahmadi, J.Timms, R.Katso, P.C.Driscoll, R.Woscholski, P.J.Parker, and M.D.Waterfield (2001).
Synthesis and function of 3-phosphorylated inositol lipids.
  Annu Rev Biochem, 70, 535-602.  
11545740 C.Mazza, M.Ohno, A.Segref, I.W.Mattaj, and S.Cusack (2001).
Crystal structure of the human nuclear cap binding complex.
  Mol Cell, 8, 383-396.
PDB code: 1h6k
11232585 D.J.Gillooly, and H.Stenmark (2001).
Cell biology. A lipid oils the endocytosis machine.
  Science, 291, 993-994.  
11454198 E.Vassella, R.Krämer, C.M.Turner, M.Wankell, C.Modes, M.van den Bogaard, and M.Boshart (2001).
Deletion of a novel protein kinase with PX and FYVE-related domains increases the rate of differentiation of Trypanosoma brucei.
  Mol Microbiol, 41, 33-46.  
11389851 H.Yamaguchi, M.Matsushita, A.C.Nairn, and J.Kuriyan (2001).
Crystal structure of the atypical protein kinase domain of a TRP channel with phosphotransferase activity.
  Mol Cell, 7, 1047-1057.
PDB codes: 1ia9 1iah 1iaj
11248547 J.H.Hurley, and T.Meyer (2001).
Subcellular targeting by membrane lipids.
  Curr Opin Cell Biol, 13, 146-152.  
11179890 J.H.Laity, B.M.Lee, and P.E.Wright (2001).
Zinc finger proteins: new insights into structural and functional diversity.
  Curr Opin Struct Biol, 11, 39-46.  
  11694590 J.Hirst, M.R.Lindsay, and M.S.Robinson (2001).
GGAs: roles of the different domains and comparison with AP-1 and clathrin.
  Mol Biol Cell, 12, 3573-3588.  
11741531 J.J.Dumas, E.Merithew, E.Sudharshan, D.Rajamani, S.Hayes, D.Lawe, S.Corvera, and D.G.Lambright (2001).
Multivalent endosome targeting by homodimeric EEA1.
  Mol Cell, 8, 947-958.
PDB code: 1joc
11454451 M.S.Robinson, and J.S.Bonifacino (2001).
Adaptor-related proteins.
  Curr Opin Cell Biol, 13, 444-453.  
11340172 M.Yamada, T.Takeshita, S.Miura, K.Murata, Y.Kimura, N.Ishii, M.Nose, H.Sakagami, H.Kondo, F.Tashiro, J.I.Miyazaki, H.Sasaki, and K.Sugamura (2001).
Loss of hippocampal CA3 pyramidal neurons in mice lacking STAM1.
  Mol Cell Biol, 21, 3807-3819.  
11292843 N.V.Grishin (2001).
Treble clef finger--a functionally diverse zinc-binding structural motif.
  Nucleic Acids Res, 29, 1703-1714.  
11230696 T.Kutateladze, and M.Overduin (2001).
Structural mechanism of endosome docking by the FYVE domain.
  Science, 291, 1793-1796.
PDB codes: 1hyi 1hyj
11239400 Y.Mao, J.Chen, J.A.Maynard, B.Zhang, and F.A.Quiocho (2001).
A novel all helix fold of the AP180 amino-terminal domain for phosphoinositide binding and clathrin assembly in synaptic vesicle endocytosis.
  Cell, 104, 433-440.
PDB code: 1hx8
10970851 D.J.Gillooly, I.C.Morrow, M.Lindsay, R.Gould, N.J.Bryant, J.M.Gaullier, R.G.Parton, and H.Stenmark (2000).
Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells.
  EMBO J, 19, 4577-4588.  
10873829 D.J.Owen, and J.P.Luzio (2000).
Structural insights into clathrin-mediated endocytosis.
  Curr Opin Cell Biol, 12, 467-474.  
11114512 J.H.Hurley, Y.Tsujishita, and M.A.Pearson (2000).
Floundering about at cell membranes: a structural view of phospholipid signaling.
  Curr Opin Struct Biol, 10, 737-743.  
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 code is shown on the right.