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PDBsum entry 2jqh

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protein links
Protein transport PDB id
2jqh
Jmol
Contents
Protein chain
72 a.a. *
* Residue conservation analysis
PDB id:
2jqh
Name: Protein transport
Title: Vps4b mit
Structure: Vacuolar protein sorting-associating protein 4b. Chain: a. Fragment: mit domain, residues 1-86. Synonym: suppressor of k+, transport growth defect 1, protein skd1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: vps4b, skd1, vps42. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 20 models
Authors: M.D.Stuchell-Brereton,J.J.Skalicky,C.Kieffer,S.Ghaffarian, W.I.Sundquist
Key ref:
M.D.Stuchell-Brereton et al. (2007). ESCRT-III recognition by VPS4 ATPases. Nature, 449, 740-744. PubMed id: 17928862 DOI: 10.1038/nature06172
Date:
01-Jun-07     Release date:   16-Oct-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O75351  (VPS4B_HUMAN) -  Vacuolar protein sorting-associated protein 4B
Seq:
Struc:
444 a.a.
72 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.6.4.6  - Vesicle-fusing ATPase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + H2O = ADP + phosphate
ATP
+ H(2)O
= ADP
+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1038/nature06172 Nature 449:740-744 (2007)
PubMed id: 17928862  
 
 
ESCRT-III recognition by VPS4 ATPases.
M.D.Stuchell-Brereton, J.J.Skalicky, C.Kieffer, M.A.Karren, S.Ghaffarian, W.I.Sundquist.
 
  ABSTRACT  
 
The ESCRT (endosomal sorting complex required for transport) pathway is required for terminal membrane fission events in several important biological processes, including endosomal intraluminal vesicle formation, HIV budding and cytokinesis. VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly, possibly in conjunction with membrane fission. Here we show that the microtubule interacting and transport (MIT) domains of human VPS4A and VPS4B bind conserved sequence motifs located at the carboxy termini of the CHMP1-3 class of ESCRT-III proteins. Structures of VPS4A MIT-CHMP1A and VPS4B MIT-CHMP2B complexes reveal that the C-terminal CHMP motif forms an amphipathic helix that binds in a groove between the last two helices of the tetratricopeptide-like repeat (TPR) of the VPS4 MIT domain, but in the opposite orientation to that of a canonical TPR interaction. Distinct pockets in the MIT domain bind three conserved leucine residues of the CHMP motif, and mutations that inhibit these interactions block VPS4 recruitment, impair endosomal protein sorting and relieve dominant-negative VPS4 inhibition of HIV budding. Thus, our studies reveal how the VPS4 ATPases recognize their CHMP substrates to facilitate the membrane fission events required for the release of viruses, endosomal vesicles and daughter cells.
 
  Selected figure(s)  
 
Figure 2.
Figure 2: Structural basis for VPS4 MIT recognition of CHMP1–3. a, Alignments of ESCRT-III protein C termini. C-terminal sequences of human proteins from the six CHMP classes are shown explicitly, together with a graph showing the degree of sequence conservation within aligned CHMP1–3 C termini (50 sequences; see Supplementary Table 2) and the consensus sequence (below the graph). Note that ESCRT-III proteins of the CHMP4–6 class do not conform to the consensus. b, Solution structure of the VPS4A MIT–CHMP1A[180–196] complex, with the three conserved CHMP1A[180–196] leucines shown explicitly. This helical colour scheme is also used in c–f. c, Structure of the VPS4A MIT–CHMP1A[180–196] complex. The MIT domain is shown in a space-filling model with Leu 64 highlighted in blue; important residues on both sides of the interface are shown explicitly. Arrows denote the approximate orientations of the three leucine-binding pockets shown in d–f. d–f, Close-up views of the three leucine-binding pockets of the VPS4A MIT domain showing the hydrophobic pocket views in detail, as well as complementary charge interactions between Glu 184 and Arg 57 (d), between Arg 195 and Glu 37 (e), and between Arg 190 and Glu 68 (Asp 65) (f); CHMP1A residues are listed first.
Figure 3.
Figure 3: The Vps4 MIT Leu64Asp mutation inhibits membrane protein sorting into the vacuolar lumen. a, Confocal fluorescence slices of live yeast cells showing localization of the model membrane protein cargo, GFP–CPS, in the presence of wild-type (WT) Vps4 (top row), no Vps4 (middle row) or Vps4[L64D] (bottom row), at 30 °C. FM4-64 staining (red) was used to define the limiting vacuolar membrane (open circles) and to reveal class E compartments (intense puncta in the middle and bottom rows). Overlaid fluorescence and differential interference contrast (DIC) images are shown in the right two columns for reference. Scale bar, 5 m. b, Graphic quantification of the experiment shown in a, demonstrating that the Vps4[L64D] mutant inhibits GFP–CPS trafficking into the lumen of the vacuole. GFP–CPS localization was examined at 30 °C (open columns) and 37 °C (filled columns). Data are from three independent experiments (100 cells per experiment); error bars indicate s.d.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2007, 449, 740-744) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23023333 G.H.Mochida, V.S.Ganesh, M.I.de Michelena, H.Dias, K.D.Atabay, K.L.Kathrein, H.T.Huang, R.S.Hill, J.M.Felie, D.Rakiec, D.Gleason, A.D.Hill, A.N.Malik, B.J.Barry, J.N.Partlow, W.H.Tan, L.J.Glader, A.J.Barkovich, W.B.Dobyns, L.I.Zon, and C.A.Walsh (2012).
CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development.
  Nat Genet, 44, 1260-1264.  
21220121 B.Różycki, Y.C.Kim, and G.Hummer (2011).
SAXS ensemble refinement of ESCRT-III CHMP3 conformational transitions.
  Structure, 19, 109-116.  
  21396898 E.Morita, V.Sandrin, J.McCullough, A.Katsuyama, I.Baci Hamilton, and W.I.Sundquist (2011).
ESCRT-III protein requirements for HIV-1 budding.
  Cell Host Microbe, 9, 235-242.  
21332354 J.H.Hurley, and H.Stenmark (2011).
Molecular mechanisms of ubiquitin-dependent membrane traffic.
  Annu Rev Biophys, 40, 119-142.  
21677686 J.Martin-Serrano, and S.J.Neil (2011).
Host factors involved in retroviral budding and release.
  Nat Rev Microbiol, 9, 519-531.  
21263029 M.Wemmer, I.Azmi, M.West, B.Davies, D.Katzmann, and G.Odorizzi (2011).
Bro1 binding to Snf7 regulates ESCRT-III membrane scission activity in yeast.
  J Cell Biol, 192, 295-306.  
21030261 S.Peel, P.Macheboeuf, N.Martinelli, and W.Weissenhorn (2011).
Divergent pathways lead to ESCRT-III-catalyzed membrane fission.
  Trends Biochem Sci, 36, 199-210.  
21394086 V.Baumgärtel, S.Ivanchenko, A.Dupont, M.Sergeev, P.W.Wiseman, H.G.Kräusslich, C.Bräuchle, B.Müller, and D.C.Lamb (2011).
Live-cell visualization of dynamics of HIV budding site interactions with an ESCRT component.
  Nat Cell Biol, 13, 469-474.  
20362686 A.Hervás-Aguilar, O.Rodríguez-Galán, A.Galindo, J.F.Abenza, H.N.Arst, and M.A.Peñalva (2010).
Characterization of Aspergillus nidulans DidB Did2, a non-essential component of the multivesicular body pathway.
  Fungal Genet Biol, 47, 636-646.  
19963362 A.Roll-Mecak, and F.J.McNally (2010).
Microtubule-severing enzymes.
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20110351 A.Shestakova, A.Hanono, S.Drosner, M.Curtiss, B.A.Davies, D.J.Katzmann, and M.Babst (2010).
Assembly of the AAA ATPase Vps4 on ESCRT-III.
  Mol Biol Cell, 21, 1059-1071.  
20702581 B.A.Davies, I.F.Azmi, J.Payne, A.Shestakova, B.F.Horazdovsky, M.Babst, and D.J.Katzmann (2010).
Coordination of substrate binding and ATP hydrolysis in Vps4-mediated ESCRT-III disassembly.
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20719964 B.Renvoisé, R.L.Parker, D.Yang, J.C.Bakowska, J.H.Hurley, and C.Blackstone (2010).
SPG20 protein spartin is recruited to midbodies by ESCRT-III protein Ist1 and participates in cytokinesis.
  Mol Biol Cell, 21, 3293-3303.  
20805499 C.Tu, C.F.Ortega-Cava, P.Winograd, M.J.Stanton, A.L.Reddi, I.Dodge, R.Arya, M.Dimri, R.J.Clubb, M.Naramura, K.U.Wagner, V.Band, and H.Band (2010).
Endosomal-sorting complexes required for transport (ESCRT) pathway-dependent endosomal traffic regulates the localization of active Src at focal adhesions.
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20134403 D.Teis, S.Saksena, B.L.Judson, and S.D.Emr (2010).
ESCRT-II coordinates the assembly of ESCRT-III filaments for cargo sorting and multivesicular body vesicle formation.
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20223751 H.Urwin, A.Authier, J.E.Nielsen, D.Metcalf, C.Powell, K.Froud, D.S.Malcolm, I.Holm, P.Johannsen, J.Brown, E.M.Fisher, J.van der Zee, M.Bruyland, C.Van Broeckhoven, J.Collinge, S.Brandner, C.Futter, and A.M.Isaacs (2010).
Disruption of endocytic trafficking in frontotemporal dementia with CHMP2B mutations.
  Hum Mol Genet, 19, 2228-2238.  
19864377 J.A.Jadwin, V.Rudd, P.Sette, S.Challa, and F.Bouamr (2010).
Late domain-independent rescue of a release-deficient Moloney murine leukemia virus by the ubiquitin ligase itch.
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20588296 J.H.Hurley, and P.I.Hanson (2010).
Membrane budding and scission by the ESCRT machinery: it's all in the neck.
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20653365 J.H.Hurley (2010).
The ESCRT complexes.
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20818414 K.S.Makarova, N.Yutin, S.D.Bell, and E.V.Koonin (2010).
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19828764 L.Corless, C.M.Crump, S.D.Griffin, and M.Harris (2010).
Vps4 and the ESCRT-III complex are required for the release of infectious hepatitis C virus particles.
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20625756 M.Ghanim, L.Guillot-Noel, F.Pasquier, L.Jornea, V.Deramecourt, B.Dubois, I.Le Ber, A.Brice, A.Brice, F.Blanc, W.Camu, F.Clerget-Darpoux, P.Corcia, M.Didic, B.Dubois, C.Duyckaerts, M.O.Habert, V.Golfier, E.Guedj, D.Hannequin, L.Lacomblez, I.Le Ber, R.Levy, V.Meininger, B.F.Michel, F.Pasquier, C.Thomas-Anterion, M.Puel, F.Salachas, F.Sellal, M.Vercelletto, and P.Verpillat (2010).
CHMP2B mutations are rare in French families with frontotemporal lobar degeneration.
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  Extremophiles, 13, 67-79.  
  19865606 A.Pincetic, and J.Leis (2009).
The Mechanism of Budding of Retroviruses From Cell Membranes.
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19535732 B.McDonald, and J.Martin-Serrano (2009).
No strings attached: the ESCRT machinery in viral budding and cytokinesis.
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Computational model of membrane fission catalyzed by ESCRT-III.
  PLoS Comput Biol, 5, e1000575.  
  20148178 H.Marjuki, U.Wernery, H.L.Yen, J.Franks, P.Seiler, D.Walker, S.Krauss, and R.G.Webster (2009).
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19000169 J.W.Connell, C.Lindon, J.P.Luzio, and E.Reid (2009).
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  Traffic, 10, 42-56.  
19477918 J.Xiao, X.W.Chen, B.A.Davies, A.R.Saltiel, D.J.Katzmann, and Z.Xu (2009).
Structural basis of Ist1 function and Ist1-Did2 interaction in the multivesicular body pathway and cytokinesis.
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PDB codes: 3ggy 3ggz
19129480 M.Agromayor, J.G.Carlton, J.P.Phelan, D.R.Matthews, L.M.Carlin, S.Ameer-Beg, K.Bowers, and J.Martin-Serrano (2009).
Essential role of hIST1 in cytokinesis.
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19129479 M.Bajorek, E.Morita, J.J.Skalicky, S.G.Morham, M.Babst, and W.I.Sundquist (2009).
Biochemical analyses of human IST1 and its function in cytokinesis.
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19525971 M.Bajorek, H.L.Schubert, J.McCullough, C.Langelier, D.M.Eckert, W.M.Stubblefield, N.T.Uter, D.G.Myszka, C.P.Hill, and W.I.Sundquist (2009).
Structural basis for ESCRT-III protein autoinhibition.
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PDB codes: 3frr 3frs 3frt 3frv
19278657 M.J.Landsberg, P.R.Vajjhala, R.Rothnagel, A.L.Munn, and B.Hankamer (2009).
Three-dimensional structure of AAA ATPase Vps4: advancing structural insights into the mechanisms of endosomal sorting and enveloped virus budding.
  Structure, 17, 427-437.  
19056728 O.Rodríguez-Galán, A.Galindo, A.Hervás-Aguilar, H.N.Arst, and M.A.Peñalva (2009).
Physiological Involvement in pH Signaling of Vps24-mediated Recruitment of Aspergillus PalB Cysteine Protease to ESCRT-III.
  J Biol Chem, 284, 4404-4412.  
19560911 P.I.Hanson, S.Shim, and S.A.Merrill (2009).
Cell biology of the ESCRT machinery.
  Curr Opin Cell Biol, 21, 568-574.  
19725809 P.Weiss, S.Huppert, and R.Kölling (2009).
Analysis of the dual function of the ESCRT-III protein Snf7 in endocytic trafficking and in gene expression.
  Biochem J, 424, 89-97.  
19158374 Q.L.Aoh, A.M.Castle, C.H.Hubbard, O.Katsumata, and J.D.Castle (2009).
SCAMP3 negatively regulates epidermal growth factor receptor degradation and promotes receptor recycling.
  Mol Biol Cell, 20, 1816-1832.  
19783442 R.Y.Samson, and S.D.Bell (2009).
Ancient ESCRTs and the evolution of binary fission.
  Trends Microbiol, 17, 507-513.  
19135892 S.Saksena, J.Wahlman, D.Teis, A.E.Johnson, and S.D.Emr (2009).
Functional reconstitution of ESCRT-III assembly and disassembly.
  Cell, 136, 97.  
19307600 S.W.Eastman, M.Yassaee, and P.D.Bieniasz (2009).
A role for ubiquitin ligases and Spartin/SPG20 in lipid droplet turnover.
  J Cell Biol, 184, 881-894.  
19580544 T.L.Edwards, V.E.Clowes, H.T.Tsang, J.W.Connell, C.M.Sanderson, J.P.Luzio, and E.Reid (2009).
Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5.
  Biochem J, 423, 31-39.  
19234443 T.Wollert, C.Wunder, J.Lippincott-Schwartz, and J.H.Hurley (2009).
Membrane scission by the ESCRT-III complex.
  Nature, 458, 172-177.  
19535731 T.Wollert, D.Yang, X.Ren, H.H.Lee, Y.J.Im, and J.H.Hurley (2009).
The ESCRT machinery at a glance.
  J Cell Sci, 122, 2163-2166.  
19282983 V.Dussupt, M.P.Javid, G.Abou-Jaoudé, J.A.Jadwin, J.de La Cruz, K.Nagashima, and F.Bouamr (2009).
The nucleocapsid region of HIV-1 Gag cooperates with the PTAP and LYPXnL late domains to recruit the cellular machinery necessary for viral budding.
  PLoS Pathog, 5, e1000339.  
19686684 Y.J.Im, T.Wollert, E.Boura, and J.H.Hurley (2009).
Structure and function of the ESCRT-II-III interface in multivesicular body biogenesis.
  Dev Cell, 17, 234-243.
PDB code: 3htu
18987308 A.C.Lindås, E.A.Karlsson, M.T.Lindgren, T.J.Ettema, and R.Bernander (2008).
A unique cell division machinery in the Archaea.
  Proc Natl Acad Sci U S A, 105, 18942-18946.  
18645585 A.E.Armitage, A.J.McMichael, and H.Drakesmith (2008).
Reflecting on a quarter century of HIV research.
  Nat Immunol, 9, 823-826.  
18606141 C.Kieffer, J.J.Skalicky, E.Morita, I.De Domenico, D.M.Ward, J.Kaplan, and W.I.Sundquist (2008).
Two distinct modes of ESCRT-III recognition are required for VPS4 functions in lysosomal protein targeting and HIV-1 budding.
  Dev Cell, 15, 62-73.
PDB code: 2k3w
18316332 C.Yorikawa, E.Takaya, Y.Osako, R.Tanaka, Y.Terasawa, T.Hamakubo, Y.Mochizuki, H.Iwanari, T.Kodama, T.Maeda, K.Hitomi, H.Shibata, and M.Maki (2008).
Human calpain 7/PalBH associates with a subset of ESCRT-III-related proteins in its N-terminal region and partly localizes to endocytic membrane compartments.
  J Biochem, 143, 731-745.  
18997780 D.Yang, N.Rismanchi, B.Renvoisé, J.Lippincott-Schwartz, C.Blackstone, and J.H.Hurley (2008).
Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B.
  Nat Struct Mol Biol, 15, 1278-1286.
PDB code: 3eab
18222686 J.H.Hurley (2008).
ESCRT complexes and the biogenesis of multivesicular bodies.
  Curr Opin Cell Biol, 20, 4.  
18511562 J.McCullough, R.D.Fisher, F.G.Whitby, W.I.Sundquist, and C.P.Hill (2008).
ALIX-CHMP4 interactions in the human ESCRT pathway.
  Proc Natl Acad Sci U S A, 105, 7687-7691.
PDB codes: 3c3o 3c3q 3c3r
18194651 J.Xiao, H.Xia, J.Zhou, I.F.Azmi, B.A.Davies, D.J.Katzmann, and Z.Xu (2008).
Structural basis of Vta1 function in the multivesicular body sorting pathway.
  Dev Cell, 14, 37-49.
PDB codes: 2rkk 2rkl
18209100 P.I.Hanson, R.Roth, Y.Lin, and J.E.Heuser (2008).
Plasma membrane deformation by circular arrays of ESCRT-III protein filaments.
  J Cell Biol, 180, 389-402.  
18266866 P.R.Vajjhala, C.H.Nguyen, M.J.Landsberg, C.Kistler, A.L.Gan, G.F.King, B.Hankamer, and A.L.Munn (2008).
The Vps4 C-terminal helix is a critical determinant for assembly and ATPase activity and has elements conserved in other members of the meiotic clade of AAA ATPases.
  FEBS J, 275, 1427-1449.  
19008417 R.Y.Samson, T.Obita, S.M.Freund, R.L.Williams, and S.D.Bell (2008).
A role for the ESCRT system in cell division in archaea.
  Science, 322, 1710-1713.
PDB code: 2w2u
18786397 S.Ghazi-Tabatabai, S.Saksena, J.M.Short, A.V.Pobbati, D.B.Veprintsev, R.A.Crowther, S.D.Emr, E.H.Egelman, and R.L.Williams (2008).
Structure and disassembly of filaments formed by the ESCRT-III subunit Vps24.
  Structure, 16, 1345-1356.  
18687924 S.Lata, G.Schoehn, A.Jain, R.Pires, J.Piehler, H.G.Gottlinger, and W.Weissenhorn (2008).
Helical structures of ESCRT-III are disassembled by VPS4.
  Science, 321, 1354-1357.  
18385515 S.Shim, S.A.Merrill, and P.I.Hanson (2008).
Novel interactions of ESCRT-III with LIP5 and VPS4 and their implications for ESCRT-III disassembly.
  Mol Biol Cell, 19, 2661-2672.  
18321969 Y.Usami, S.Popov, E.Popova, and H.G.Göttlinger (2008).
Efficient and specific rescue of human immunodeficiency virus type 1 budding defects by a Nedd4-like ubiquitin ligase.
  J Virol, 82, 4898-4907.  
18280501 Z.Yu, M.D.Gonciarz, W.I.Sundquist, C.P.Hill, and G.J.Jensen (2008).
Cryo-EM structure of dodecameric Vps4p and its 2:1 complex with Vta1p.
  J Mol Biol, 377, 364-377.  
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.