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| | ==Integrated structural and functional model of the human ESCRT-II complex== | | ==Integrated structural and functional model of the human ESCRT-II complex== |
| - | <StructureSection load='3cuq' size='340' side='right' caption='[[3cuq]], [[Resolution|resolution]] 2.61Å' scene=''> | + | <StructureSection load='3cuq' size='340' side='right'caption='[[3cuq]], [[Resolution|resolution]] 2.61Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3cuq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CUQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CUQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3cuq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CUQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CUQ FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zme|2zme]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2zme|2zme]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SNF8, EAP30 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), VPS36, C13orf9, EAP45 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), VPS25, DERP9, EAP20 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SNF8, EAP30 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), VPS36, C13orf9, EAP45 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), VPS25, DERP9, EAP20 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3cuq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cuq OCA], [http://pdbe.org/3cuq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cuq RCSB], [http://www.ebi.ac.uk/pdbsum/3cuq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3cuq ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3cuq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cuq OCA], [https://pdbe.org/3cuq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cuq RCSB], [https://www.ebi.ac.uk/pdbsum/3cuq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cuq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SNF8_HUMAN SNF8_HUMAN]] Component of the endosomal sorting complex required for transport II (ESCRT-II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. The ESCRT-II complex may also play a role in transcription regulation by participating in derepression of transcription by RNA polymerase II, possibly via its interaction with ELL. Required for degradation of both endocytosed EGF and EGFR, but not for the EGFR ligand-mediated internalization. It is also required for the degradation of CXCR4.<ref>PMID:17959629</ref> <ref>PMID:17714434</ref> <ref>PMID:18031739</ref> [[http://www.uniprot.org/uniprot/VPS25_HUMAN VPS25_HUMAN]] Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. The ESCRT-II complex may also play a role in transcription regulation, possibly via its interaction with ELL. The ESCRT-II complex may be involved in facilitating the budding of certain RNA viruses.<ref>PMID:18723511</ref> [[http://www.uniprot.org/uniprot/VPS36_HUMAN VPS36_HUMAN]] Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. Its ability to bind ubiquitin probably plays a role in endosomal sorting of ubiquitinated cargo proteins by ESCRT complexes. The ESCRT-II complex may also play a role in transcription regulation, possibly via its interaction with ELL. Binds phosphoinosides such as PtdIns(3,4,5)P3.<ref>PMID:15755741</ref> | + | [[https://www.uniprot.org/uniprot/SNF8_HUMAN SNF8_HUMAN]] Component of the endosomal sorting complex required for transport II (ESCRT-II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. The ESCRT-II complex may also play a role in transcription regulation by participating in derepression of transcription by RNA polymerase II, possibly via its interaction with ELL. Required for degradation of both endocytosed EGF and EGFR, but not for the EGFR ligand-mediated internalization. It is also required for the degradation of CXCR4.<ref>PMID:17959629</ref> <ref>PMID:17714434</ref> <ref>PMID:18031739</ref> [[https://www.uniprot.org/uniprot/VPS25_HUMAN VPS25_HUMAN]] Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. The ESCRT-II complex may also play a role in transcription regulation, possibly via its interaction with ELL. The ESCRT-II complex may be involved in facilitating the budding of certain RNA viruses.<ref>PMID:18723511</ref> [[https://www.uniprot.org/uniprot/VPS36_HUMAN VPS36_HUMAN]] Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. Its ability to bind ubiquitin probably plays a role in endosomal sorting of ubiquitinated cargo proteins by ESCRT complexes. The ESCRT-II complex may also play a role in transcription regulation, possibly via its interaction with ELL. Binds phosphoinosides such as PtdIns(3,4,5)P3.<ref>PMID:15755741</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3cuq" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3cuq" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Vacuolar protein sorting-associated protein 3D structures|Vacuolar protein sorting-associated protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Hurley, J H]] | | [[Category: Hurley, J H]] |
| | [[Category: Im, Y J]] | | [[Category: Im, Y J]] |
| Structural highlights
3cuq is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | |
| Gene: | SNF8, EAP30 (HUMAN), VPS36, C13orf9, EAP45 (HUMAN), VPS25, DERP9, EAP20 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[SNF8_HUMAN] Component of the endosomal sorting complex required for transport II (ESCRT-II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. The ESCRT-II complex may also play a role in transcription regulation by participating in derepression of transcription by RNA polymerase II, possibly via its interaction with ELL. Required for degradation of both endocytosed EGF and EGFR, but not for the EGFR ligand-mediated internalization. It is also required for the degradation of CXCR4.[1] [2] [3] [VPS25_HUMAN] Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. The ESCRT-II complex may also play a role in transcription regulation, possibly via its interaction with ELL. The ESCRT-II complex may be involved in facilitating the budding of certain RNA viruses.[4] [VPS36_HUMAN] Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. Its ability to bind ubiquitin probably plays a role in endosomal sorting of ubiquitinated cargo proteins by ESCRT complexes. The ESCRT-II complex may also play a role in transcription regulation, possibly via its interaction with ELL. Binds phosphoinosides such as PtdIns(3,4,5)P3.[5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
ESCRT-II plays a pivotal role in receptor downregulation and multivesicular body biogenesis and is conserved from yeast to humans. The crystal structures of two human ESCRT-II complex structures have been determined at 2.6 and 2.9 A resolution, respectively. The complex has three lobes and contains one copy each of VPS22 and VPS36 and two copies of VPS25. The structure reveals a dynamic helical domain to which both the VPS22 and VPS36 subunits contribute that connects the GLUE domain to the rest of the ESCRT-II core. Hydrodynamic analysis shows that intact ESCRT-II has a compact, closed conformation. ESCRT-II binds to the ESCRT-I VPS28 C-terminal domain subunit through a helix immediately C-terminal to the VPS36-GLUE domain. ESCRT-II is targeted to endosomal membranes by the lipid-binding activities of both the Vps36 GLUE domain and the first helix of Vps22. These data provide a unifying structural and functional framework for the ESCRT-II complex.
Integrated structural model and membrane targeting mechanism of the human ESCRT-II complex.,Im YJ, Hurley JH Dev Cell. 2008 Jun;14(6):902-13. PMID:18539118[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Progida C, Malerod L, Stuffers S, Brech A, Bucci C, Stenmark H. RILP is required for the proper morphology and function of late endosomes. J Cell Sci. 2007 Nov 1;120(Pt 21):3729-37. PMID:17959629 doi:http://dx.doi.org/10.1242/jcs.017301
- ↑ Malerod L, Stuffers S, Brech A, Stenmark H. Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth factor and chemokine receptors destined for lysosomal degradation. Traffic. 2007 Nov;8(11):1617-29. Epub 2007 Aug 20. PMID:17714434 doi:http://dx.doi.org/10.1111/j.1600-0854.2007.00630.x
- ↑ Raiborg C, Malerod L, Pedersen NM, Stenmark H. Differential functions of Hrs and ESCRT proteins in endocytic membrane trafficking. Exp Cell Res. 2008 Feb 15;314(4):801-13. Epub 2007 Nov 26. PMID:18031739 doi:http://dx.doi.org/10.1016/j.yexcr.2007.10.014
- ↑ Pincetic A, Medina G, Carter C, Leis J. Avian sarcoma virus and human immunodeficiency virus, type 1 use different subsets of ESCRT proteins to facilitate the budding process. J Biol Chem. 2008 Oct 31;283(44):29822-30. doi: 10.1074/jbc.M804157200. Epub 2008, Aug 22. PMID:18723511 doi:http://dx.doi.org/10.1074/jbc.M804157200
- ↑ Slagsvold T, Aasland R, Hirano S, Bache KG, Raiborg C, Trambaiolo D, Wakatsuki S, Stenmark H. Eap45 in mammalian ESCRT-II binds ubiquitin via a phosphoinositide-interacting GLUE domain. J Biol Chem. 2005 May 20;280(20):19600-6. Epub 2005 Mar 7. PMID:15755741 doi:http://dx.doi.org/10.1074/jbc.M501510200
- ↑ Im YJ, Hurley JH. Integrated structural model and membrane targeting mechanism of the human ESCRT-II complex. Dev Cell. 2008 Jun;14(6):902-13. PMID:18539118 doi:10.1016/j.devcel.2008.04.004
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