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PDBsum entry 1xwi

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Protein transport PDB id
1xwi
Jmol
Contents
Protein chain
322 a.a. *
Ligands
SO4 ×2
Waters ×9
* Residue conservation analysis
PDB id:
1xwi
Name: Protein transport
Title: Crystal structure of vps4b
Structure: Skd1 protein. Chain: a. Fragment: residues 123-444. Synonym: vacuolar sorting protein 4b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: vps4b, skd1, vps42. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.80Å     R-factor:   0.199     R-free:   0.260
Authors: A.Scott,W.I.Sundquist,C.P.Hill
Key ref:
A.Scott et al. (2005). Structural and mechanistic studies of VPS4 proteins. EMBO J, 24, 3658-3669. PubMed id: 16193069 DOI: 10.1038/sj.emboj.7600818
Date:
01-Nov-04     Release date:   11-Oct-05    
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.
322 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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     nucleotide binding     3 terms  

 

 
    reference    
 
 
DOI no: 10.1038/sj.emboj.7600818 EMBO J 24:3658-3669 (2005)
PubMed id: 16193069  
 
 
Structural and mechanistic studies of VPS4 proteins.
A.Scott, H.Y.Chung, M.Gonciarz-Swiatek, G.C.Hill, F.G.Whitby, J.Gaspar, J.M.Holton, R.Viswanathan, S.Ghaffarian, C.P.Hill, W.I.Sundquist.
 
  ABSTRACT  
 
VPS4 ATPases function in multivesicular body formation and in HIV-1 budding. Here, we report the crystal structure of monomeric apo human VPS4B/SKD1 (hVPS4B), which is composed of five distinct elements: a poorly ordered N-terminal MIT domain that binds ESCRT-III substrates, large (mixed alpha/beta) and small (alpha) AAA ATPase domains that closely resemble analogous domains in the p97 D1 ATPase cassette, a three-stranded antiparallel beta domain inserted within the small ATPase domain, and a novel C-terminal helix. Apo hVPS4B and yeast Vps4p (yVps4p) proteins dimerized in solution, and assembled into larger complexes (10-12 subunits) upon ATP binding. Human and yeast adaptor proteins (LIP5 and yVta1p, respectively) bound the beta domains of the fully assembled hVPS4B and yVps4p proteins. We therefore propose that Vps4 proteins cycle between soluble, inactive low molecular weight complexes and active, membrane-associated double-ring structures that bind ATP and coassemble with LIP5/Vta1. Finally, HIV-1 budding was inhibited by mutations in a loop that projects into the center of the modeled hVPS4B rings, suggesting that hVPS4B may release the assembled ESCRT machinery by pulling ESCRT-III substrates up into the central pore.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Structure of hVPS4B. (A) Domain map and numbering scheme for hVPS4B. The domain color coding scheme shown here is also used in Figures 2A, B, and 6. (B) Ribbon diagram (stereoview) of the hVPS4B[123-444] structure. Note that the 2/ 3 and 3/ 4 loops were not defined by experimental density (dashed lines).
Figure 6.
Figure 6 Model for the functional cycle of VPS4 proteins. Left: At steady state, hVPS4B is primarily a monomeric cytoplasmic protein (Fujita et al, 2004), and exhibits a monomer-dimer equilibrium in the absence of bound nucleotide (Babst et al, 1998; Supplementary Figure S3). LIP5/Vta1p is an oligomer of uncertain stoichiometry. Middle: Vps4 proteins are recruited to sites of vesicle formation at the endosomal membrane by interactions between the N-terminal MIT domain and the C-proximal domains of assembled ESCRT-III lattice/cage (Babst et al, 2002; Lin et al, 2005; Scott et al, 2005). The assembled Vps4 proteins can also bind ATP and LIP5/Vta1p oligomers via domain interactions to form an enzymatically active complex. Note that a head-to-tail orientation of the two Vps4 rings (not shown) is equally consistent with our data. Right: We propose that bound ESCRT-III subunits are freed from the assembled lattice/cage and released into the cytoplasm as they are pulled up into the narrow central chamber of the hVPS4B ring.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2005, 24, 3658-3669) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21677686 J.Martin-Serrano, and S.J.Neil (2011).
Host factors involved in retroviral budding and release.
  Nat Rev Microbiol, 9, 519-531.  
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.  
19963362 A.Roll-Mecak, and F.J.McNally (2010).
Microtubule-severing enzymes.
  Curr Opin Cell Biol, 22, 96.  
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.
  Mol Biol Cell, 21, 3396-3408.  
19887446 C.Zhao, E.A.Matveeva, Q.Ren, and S.W.Whiteheart (2010).
Dissecting the N-ethylmaleimide-sensitive factor: required elements of the N and D1 domains.
  J Biol Chem, 285, 761-772.  
20696398 D.Yang, and J.H.Hurley (2010).
Structural role of the Vps4-Vta1 interface in ESCRT-III recycling.
  Structure, 18, 976-984.
PDB code: 3mhv
20222872 I.Roxrud, H.Stenmark, and L.Malerød (2010).
ESCRT & Co.
  Biol Cell, 102, 293-318.  
20588296 J.H.Hurley, and P.I.Hanson (2010).
Membrane budding and scission by the ESCRT machinery: it's all in the neck.
  Nat Rev Mol Cell Biol, 11, 556-566.  
20653365 J.H.Hurley (2010).
The ESCRT complexes.
  Crit Rev Biochem Mol Biol, 45, 463-487.  
20358264 M.Boone, A.Mobasheri, R.A.Fenton, B.W.van Balkom, R.Wismans, C.E.van der Zee, and P.M.Deen (2010).
The lysosomal trafficking regulator interacting protein-5 localizes mainly in epithelial cells.
  J Mol Histol, 41, 61-74.  
20849418 Y.Osako, Y.Maemoto, R.Tanaka, H.Suzuki, H.Shibata, and M.Maki (2010).
Autolytic activity of human calpain 7 is enhanced by ESCRT-III-related protein IST1 through MIT-MIM interaction.
  FEBS J, 277, 4412-4426.  
19535732 B.McDonald, and J.Martin-Serrano (2009).
No strings attached: the ESCRT machinery in viral budding and cytokinesis.
  J Cell Sci, 122, 2167-2177.  
19194501 L.M.Rodahl, K.Haglund, C.Sem-Jacobsen, F.Wendler, J.P.Vincent, K.Lindmo, T.E.Rusten, and H.Stenmark (2009).
Disruption of Vps4 and JNK function in Drosophila causes tumour growth.
  PLoS ONE, 4, e4354.  
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.
  Mol Biol Cell, 20, 1374-1387.  
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.
  Mol Biol Cell, 20, 1360-1373.  
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.  
19783442 R.Y.Samson, and S.D.Bell (2009).
Ancient ESCRTs and the evolution of binary fission.
  Trends Microbiol, 17, 507-513.  
18202664 A.Roll-Mecak, and R.D.Vale (2008).
Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin.
  Nature, 451, 363-367.
PDB code: 3b9p
18063004 B.J.Chen, and R.A.Lamb (2008).
Mechanisms for enveloped virus budding: can some viruses do without an ESCRT?
  Virology, 372, 221-232.  
18032582 C.Dimaano, C.B.Jones, A.Hanono, M.Curtiss, and M.Babst (2008).
Ist1 regulates vps4 localization and assembly.
  Mol Biol Cell, 19, 465-474.  
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.  
18410514 D.V.Pantakani, L.S.Swapna, N.Srinivasan, and A.U.Mannan (2008).
Spastin oligomerizes into a hexamer and the mutant spastin (E442Q) redistribute the wild-type spastin into filamentous microtubule.
  J Neurochem, 106, 613-624.  
18222686 J.H.Hurley (2008).
ESCRT complexes and the biogenesis of multivesicular bodies.
  Curr Opin Cell Biol, 20, 4.  
18043242 J.Kaplan, I.De Domenico, and D.M.Ward (2008).
Chediak-Higashi syndrome.
  Curr Opin Hematol, 15, 22-29.  
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
18929572 M.D.Gonciarz, F.G.Whitby, D.M.Eckert, C.Kieffer, A.Heroux, W.I.Sundquist, and C.P.Hill (2008).
Biochemical and structural studies of yeast Vps4 oligomerization.
  J Mol Biol, 384, 878-895.
PDB codes: 3eie 3eih
18429951 N.Tanaka, M.Kyuuma, and K.Sugamura (2008).
Endosomal sorting complex required for transport proteins in cancer pathogenesis, vesicular transport, and non-endosomal functions.
  Cancer Sci, 99, 1293-1303.  
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.  
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.  
18032584 S.M.Rue, S.Mattei, S.Saksena, and S.D.Emr (2008).
Novel ist1-did2 complex functions at a late step in multivesicular body sorting.
  Mol Biol Cell, 19, 475-484.  
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.  
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.  
17696968 A.Galindo, A.Hervás-Aguilar, O.Rodríguez-Galán, O.Vincent, H.N.Arst, J.Tilburn, and M.A.Peñalva (2007).
PalC, one of two Bro1 domain proteins in the fungal pH signalling pathway, localizes to cortical structures and binds Vps32.
  Traffic, 8, 1346-1364.  
17603537 D.P.Nickerson, M.R.Russell, and G.Odorizzi (2007).
A concentric circle model of multivesicular body cargo sorting.
  EMBO Rep, 8, 644-650.  
17949747 J.Xiao, H.Xia, K.Yoshino-Koh, J.Zhou, and Z.Xu (2007).
Structural characterization of the ATPase reaction cycle of endosomal AAA protein Vps4.
  J Mol Biol, 374, 655-670.
PDB codes: 2qp9 2qpa
17928862 M.D.Stuchell-Brereton, J.J.Skalicky, C.Kieffer, M.A.Karren, S.Ghaffarian, and W.I.Sundquist (2007).
ESCRT-III recognition by VPS4 ATPases.
  Nature, 449, 740-744.
PDB codes: 2jq9 2jqh 2jqk
18023171 P.A.Tucker, and L.Sallai (2007).
The AAA+ superfamily--a myriad of motions.
  Curr Opin Struct Biol, 17, 641-652.  
17408385 P.R.Vajjhala, E.Catchpoole, C.H.Nguyen, C.Kistler, and A.L.Munn (2007).
Vps4 regulates a subset of protein interactions at the multivesicular endosome.
  FEBS J, 274, 1894-1907.  
17506697 R.C.Piper, and D.J.Katzmann (2007).
Biogenesis and function of multivesicular bodies.
  Annu Rev Cell Dev Biol, 23, 519-547.  
17450176 R.L.Williams, and S.Urbé (2007).
The emerging shape of the ESCRT machinery.
  Nat Rev Mol Cell Biol, 8, 355-368.  
17420465 S.Krebs, I.Medugorac, S.Röther, K.Strässer, and M.Förster (2007).
A missense mutation in the 3-ketodihydrosphingosine reductase FVT1 as candidate causal mutation for bovine spinal muscular atrophy.
  Proc Natl Acad Sci U S A, 104, 6746-6751.  
17325726 S.P.Goff (2007).
Host factors exploited by retroviruses.
  Nat Rev Microbiol, 5, 253-263.  
17897320 S.R.White, and B.Lauring (2007).
AAA+ ATPases: achieving diversity of function with conserved machinery.
  Traffic, 8, 1657-1667.  
17389232 S.R.White, K.J.Evans, J.Lary, J.L.Cole, and B.Lauring (2007).
Recognition of C-terminal amino acids in tubulin by pore loops in Spastin is important for microtubule severing.
  J Cell Biol, 176, 995.  
17547705 S.Shim, L.A.Kimpler, and P.I.Hanson (2007).
Structure/function analysis of four core ESCRT-III proteins reveals common regulatory role for extreme C-terminal domain.
  Traffic, 8, 1068-1079.  
17928861 T.Obita, S.Saksena, S.Ghazi-Tabatabai, D.J.Gill, O.Perisic, S.D.Emr, and R.L.Williams (2007).
Structural basis for selective recognition of ESCRT-III by the AAA ATPase Vps4.
  Nature, 449, 735-739.
PDB codes: 2v6x 2v6y
17550307 Y.Fang, N.Wu, X.Gan, W.Yan, J.C.Morrell, and S.J.Gould (2007).
Higher-order oligomerization targets plasma membrane proteins and HIV gag to exosomes.
  PLoS Biol, 5, e158.  
16615893 H.Teo, D.J.Gill, J.Sun, O.Perisic, D.B.Veprintsev, Y.Vallis, S.D.Emr, and R.L.Williams (2006).
ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes.
  Cell, 125, 99.
PDB codes: 2cay 2caz
16505166 I.Azmi, B.Davies, C.Dimaano, J.Payne, D.Eckert, M.Babst, and D.J.Katzmann (2006).
Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1.
  J Cell Biol, 172, 705-717.  
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.  
16601096 J.M.Lottridge, A.R.Flannery, J.L.Vincelli, and T.H.Stevens (2006).
Vta1p and Vps46p regulate the membrane association and ATPase activity of Vps4p at the yeast multivesicular body.
  Proc Natl Acad Sci U S A, 103, 6202-6207.  
17018057 K.Shiozawa, N.Goda, T.Shimizu, K.Mizuguchi, N.Kondo, N.Shimozawa, M.Shirakawa, and H.Hiroaki (2006).
The common phospholipid-binding activity of the N-terminal domains of PEX1 and VCP/p97.
  FEBS J, 273, 4959-4971.  
16760479 M.Agromayor, and J.Martin-Serrano (2006).
Interaction of AMSH with ESCRT-III and deubiquitination of endosomal cargo.
  J Biol Chem, 281, 23083-23091.  
16781134 M.R.Russell, D.P.Nickerson, and G.Odorizzi (2006).
Molecular mechanisms of late endosome morphology, identity and sorting.
  Curr Opin Cell Biol, 18, 422-428.  
16704411 P.R.Vajjhala, J.S.Wong, H.Y.To, and A.L.Munn (2006).
The beta domain is required for Vps4p oligomerization into a functionally active ATPase.
  FEBS J, 273, 2357-2373.  
17145965 T.Chu, J.Sun, S.Saksena, and S.D.Emr (2006).
New component of ESCRT-I regulates endosomal sorting complex assembly.
  J Cell Biol, 175, 815-823.  
16716591 T.Slagsvold, K.Pattni, L.Malerød, and H.Stenmark (2006).
Endosomal and non-endosomal functions of ESCRT proteins.
  Trends Cell Biol, 16, 317-326.  
16488176 V.Winter, and M.T.Hauser (2006).
Exploring the ESCRTing machinery in eukaryotes.
  Trends Plant Sci, 11, 115-123.  
  16293194 S.M.Barry, M.Melar, P.Gallay, and T.J.Hope (2005).
Review of the twelfth West Coast Retrovirus Meeting.
  Retrovirology, 2, 72.  
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.