FunctionVacuolar protein sorting-associated protein (Vps) are part of Endosomal Sorting Complex Required for Transport (ESCRT) that performs the topologically unique membrane bending and scission reaction away from the cytoplasm. This process is required for the multivesicular body (MVP) pathway, cytokinesis and HIV budding. There are five distinct ESCRT complexes (0,I,II,III,Vps4) with distinct functions[1].
- Vps4, Vps4A, Vps4B complex catalyzes the disassembly of the ESCRT-III filament in an ATP-driven reaction. Vps4 proteins are required for centrosome and spindle maintenance[2].
- Vps9A activates Rab5 to GTP-bound form[3].
- Vps15 may function as a G protein β subunit at the endosome [4].
- Vps23 is involved in appropriate sorting of receptors within the yast endocytic pathway and is part of the ESCRT-I complex[5]
- Vps25 is part of the ESCRT-II complex which contains two copies of the protein. It induces a conformational switch that converts inactive Vps20 into an active nucleator for Snf7 oligomerization[6].
- Vps26A and Vps26B are part of the Vps29-Vps35-Vps26 retromer which mediates transport of transmembrane proteins from endosomes to the trans-Golgi network[7].
- Vps27 interacts with the lipid phosphatidylinositol-3-phosphate and this interaction activates the MVP sorting pathway. Vps27 is part of the ESCRT-I complex[8].
- Vps28 C-terminal links ESCRT-I and ESCRT-II[9].
- Vps29, Vps30 and Vps35 are required for the recycling of Vps10p from the prevacuolar endosome back to the Golgi[10].
- Vps33 binds SNARE domains[11].
- Vps33A is part of the homotypic fusion and vacuole sorting comples which is required for fusion of intracellular compartments with lysosomes[12].
- Vps36 is part of the ESCRT-II complex
DiseaseRelevanceVps25 in Drosophila possesses several properties of tumor repressor[13].
Structural highlights | |
3D structures of vacuolar protein sorting-associated protein3D structures of vacuolar protein sorting-associated protein
Updated on 11-December-2018
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- Vps4
- 5xmi – yVps4 + ATP – yeast - Cryo EM
- 2rko – yVps4 AAA ATPase domain 124-437
- 3eie – yVps4 AAA ATPase domain (mutant) 124-437
- 3eih – yVps4 AAA ATPase domain (mutant) 124-437 + ATPgS
- 2qp9 – yVps4 83-437
- 2qpa – yVps4 (mutant) 83-437 + ADP
- 2v6x – yVps4 MIT domain 1-82 + yVps2 C-terminal
- 4niq, 5fvk – yVps4 MIT domain + yVfa1 MIM2 domain
- 5fvl – yVps4 MIT domain + yVPS20
- 3mhv – yVps4 + yVps Vta1
- 6ap1 – yVps4 + yVps Vta1 + peptide
- 5uie – yVps4 + yVps2 + yVps Vta1 – Cryo EM
- 5xmk – yVps4 + yVps Vta1 + ATP – Cryo EM
- 6bmf – yVps4 AAA ATPase domain + yVps2P – Cryo EM
- Vps4A
- 1yxr – hVps4A MIT domain – human - NMR
- 2jq9 – hVps4A MIT domain + CHMP1A peptide - NMR
- 2k3w – yVps4A MIT domain + CHMP6 peptide - NMR
- Vps4B or Skd1
- 2jqh, 2cpt, 1wr0 – hVps4B MIT domain - NMR
- 1xwi – hVps4B C-terminal
- 4u7y – hVps4B MIT domain + IST1 peptide
- 2jqk – hVps4B MIT domain + CHMP2B
- 2zam – mVps4B - mouse
- 2zao – mVps4B + ADP
- 2zan – mVps4B + ATP
- Vps9
- 1mn3 – yVps9 CUE domain 398-451
- 1p3q – yVps9 CUE domain + ubiquitin
- Vps9A
- 4g01 – Vps9A + RABF2B – Arabidopsis thaliana
- Vps13
- 6cbc – CtVps13 N-terminal (mutant) – Chaetomium thermophilum
- Vps15 or serine/threonine protein kinase Vps15
- 3gre – yVps15 WD repeat domain
- Vps23
- 2f6m – yVps23 C-terminal (mutant) + yVps28 N-terminal
- 3r42 – yVps23 N-terminal (mutant) + yVps27 peptide
- 2caz – yVps23 + yVps28 N-terminal + SRN2
- 2f66 – yVps23 C-terminal + yVps28 N-terminal + SRN2
- 2p22 – yVps23 + yVps28 N-terminal + SRN2 + peptide
- 1uzx – yVps23 UEV domain 1-161 + ubiquitin
- Vps25
- 3htu – hVps23 C-terminal WH2 domain + hVps20 first helix
- Vps26A
- 6md5 – Vps26A – zebrafish
- 4p2a – mVps26A + sorting nexin-3
- Vps26B
- Vps27
- 2pjw – yVps27 C-terminal + protein
- Vps28
- Vps29
- 3psn, 3pso – mVps29
- 5w8m – CtVps29
- 6h7w – CtVps29 + CtVps35 + CtVps26-like + CtVPS - Cryo EM
- 2r17 – yVps29 + yVps35
- 5wyh – hVps29 + interaptin
- 5osh, 5osi – hVps29 + hVps35 + interaptin
- 5gtu – hVps29 + TBC1D5
- 5xce, 5xch – EhVps29 – Entamoeba histolytica
- 5xcj, 5xck – EhVps29 (mutant)
- Vps30
- Vps33
- 5bv1 – CtVps33 + CtVps16
- 5bv0 – CtVps33 + CtVps16
- Vps33A
- 4bx8 – hVps33A
- 4bx9 – hVps33A + hVps16 C-terminal + SNARE domain
- Vps34
- 5dfz – yVps34 + yVps38 + yVps15 + yVps30 + nanobody
- Vps35
- 5f0k – hVps35 N-terminal
- 5f0j – hVps35 + hVps26A + sorting nexin-3
- 5f0l, 5f0m, 5f0p – hVps35 + hVps26A + sorting nexin-3 + DMT-1
- Vps36
- 5kc2 – yVps36 + yVps15
- 2hth – hVps36 GLUE domain 1-138 + ubiquitin
- 2zme, 3cuq – hVps36 + hVps25 + SNF8
- Vps46
- 3ggz – yVps46 MIM motif 176-204 + IST1
- Vps53
- Vps54
- 3n1b – yVps54 C-terminal
- 3n1e – mVps54 C-terminal
- Vps60
- 2luh – yVps60 + yVps Vta1 - NMR
- Vps72
- 6gej, 6gen – yVps72 + histones H3 + H4 + H2A.1 + H2B.1 + DNA + Swr1 + Arp6 + RuvbL1 + RuvbL2 + Swr complex protein 6 – Cryo EM
- Vps72 homolog
- 5chl – Vps72 + histone H2A.Z – Drosophila melanogaster
- 5fug – hVps72 N-terminal + histone H2A.Z
- Vps74
- Vps75
- 3c9b, 3c9d, 5agc – yVps75
- 3dm7 – yVps75 (mutant)
- 2zd7 – yVps75 + peptide
- 3q68, 3q66 – yVps75 + histone acetyltransferase
- 3q33 – yVps75 + histone acetyltransferase + histone H3 peptide
- 3q35 – yVps75 + histone acetyltransferase + acetyl CoA
- 5yps – Vps75 (mutant) – Pneumocystis carinii
- Vps Vta1 or Lip5
- 2lxl – hVps Vta1
- 4txp – hVps Vta1 N-terminal
- 2rkk – yVps Vta1 N-terminal
- 2rkl – yVps Vta1 C-terminal
- 5h7p – yVps Vta1 N-terminal + yVps46 D1-D2 domain - NMR
- 4u7e – hVps Vta1 N-terminal + IST1
- 2lxm – hVps Vta1 N-terminal + CHMP5
- 4txq – hVps Vta1 N-terminal + CHMP1B
- 4txr – hVps Vta1 N-terminal + CHMP1B + CHMP5
ReferencesReferences
- ↑ Schmidt O, Teis D. The ESCRT machinery. Curr Biol. 2012 Feb 21;22(4):R116-20. doi: 10.1016/j.cub.2012.01.028. PMID:22361144 doi:http://dx.doi.org/10.1016/j.cub.2012.01.028
- ↑ Morita E, Colf LA, Karren MA, Sandrin V, Rodesch CK, Sundquist WI. Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):12889-94. doi:, 10.1073/pnas.1005938107. Epub 2010 Jun 29. PMID:20616062 doi:http://dx.doi.org/10.1073/pnas.1005938107
- ↑ Goh T, Uchida W, Arakawa S, Ito E, Dainobu T, Ebine K, Takeuchi M, Sato K, Ueda T, Nakano A. VPS9a, the common activator for two distinct types of Rab5 GTPases, is essential for the development of Arabidopsis thaliana. Plant Cell. 2007 Nov;19(11):3504-15. Epub 2007 Nov 30. PMID:18055610 doi:10.1105/tpc.107.053876
- ↑ Heenan EJ, Vanhooke JL, Temple BR, Betts L, Sondek JE, Dohlman HG. Structure and function of Vps15 in the endosomal G protein signaling pathway. Biochemistry. 2009 Jul 14;48(27):6390-401. PMID:19445518 doi:10.1021/bi900621w
- ↑ Bishop N, Woodman P. TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes. J Biol Chem. 2001 Apr 13;276(15):11735-42. Epub 2000 Dec 27. PMID:11134028 doi:http://dx.doi.org/10.1074/jbc.M009863200
- ↑ Teis D, Saksena S, Judson BL, Emr SD. ESCRT-II coordinates the assembly of ESCRT-III filaments for cargo sorting and multivesicular body vesicle formation. EMBO J. 2010 Mar 3;29(5):871-83. doi: 10.1038/emboj.2009.408. Epub 2010 Feb 4. PMID:20134403 doi:http://dx.doi.org/10.1038/emboj.2009.408
- ↑ Bugarcic A, Zhe Y, Kerr MC, Griffin J, Collins BM, Teasdale RD. Vps26A and Vps26B subunits define distinct retromer complexes. Traffic. 2011 Dec;12(12):1759-73. doi: 10.1111/j.1600-0854.2011.01284.x. Epub, 2011 Oct 17. PMID:21920005 doi:http://dx.doi.org/10.1111/j.1600-0854.2011.01284.x
- ↑ Katzmann DJ, Stefan CJ, Babst M, Emr SD. Vps27 recruits ESCRT machinery to endosomes during MVB sorting. J Cell Biol. 2003 Aug 4;162(3):413-23. PMID:12900393 doi:http://dx.doi.org/10.1083/jcb.200302136
- ↑ Gill DJ, Teo H, Sun J, Perisic O, Veprintsev DB, Emr SD, Williams RL. Structural insight into the ESCRT-I/-II link and its role in MVB trafficking. EMBO J. 2007 Jan 24;26(2):600-12. Epub 2007 Jan 11. PMID:17215868
- ↑ Seaman MN, Marcusson EG, Cereghino JL, Emr SD. Endosome to Golgi retrieval of the vacuolar protein sorting receptor, Vps10p, requires the function of the VPS29, VPS30, and VPS35 gene products. J Cell Biol. 1997 Apr 7;137(1):79-92. PMID:9105038
- ↑ Lobingier BT, Merz AJ. Sec1/Munc18 protein Vps33 binds to SNARE domains and the quaternary SNARE complex. Mol Biol Cell. 2012 Dec;23(23):4611-22. doi: 10.1091/mbc.E12-05-0343. Epub 2012, Oct 10. PMID:23051737 doi:http://dx.doi.org/10.1091/mbc.E12-05-0343
- ↑ Wartosch L, Gunesdogan U, Graham SC, Luzio JP. Recruitment of VPS33A to HOPS by VPS16 Is Required for Lysosome Fusion with Endosomes and Autophagosomes. Traffic. 2015 Jul;16(7):727-42. doi: 10.1111/tra.12283. Epub 2015 Apr 30. PMID:25783203 doi:http://dx.doi.org/10.1111/tra.12283
- ↑ Thompson BJ, Mathieu J, Sung HH, Loeser E, Rorth P, Cohen SM. Tumor suppressor properties of the ESCRT-II complex component Vps25 in Drosophila. Dev Cell. 2005 Nov;9(5):711-20. doi: 10.1016/j.devcel.2005.09.020. PMID:16256745 doi:http://dx.doi.org/10.1016/j.devcel.2005.09.020
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