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| - | [[Image:2r03.jpg|left|200px]] | |
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| - | {{Structure
| + | ==Crystal Structure of ALIX/AIP1 in complex with the YPDL Late Domain== |
| - | |PDB= 2r03 |SIZE=350|CAPTION= <scene name='initialview01'>2r03</scene>, resolution 2.590Å
| + | <StructureSection load='2r03' size='340' side='right'caption='[[2r03]], [[Resolution|resolution]] 2.59Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND=
| + | <table><tr><td colspan='2'>[[2r03]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Equine_infectious_anemia_virus_(ISOLATE_WYOMING) Equine infectious anemia virus (ISOLATE WYOMING)] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R03 FirstGlance]. <br> |
| - | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.59Å</td></tr> |
| - | |GENE= PDCD6IP, AIP1, ALIX, KIAA1375 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2r03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r03 OCA], [https://pdbe.org/2r03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r03 RCSB], [https://www.ebi.ac.uk/pdbsum/2r03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r03 ProSAT]</span></td></tr> |
| - | }}
| + | </table> |
| - | | + | == Function == |
| - | '''Crystal Structure of ALIX/AIP1 in complex with the YPDL Late Domain''' | + | [https://www.uniprot.org/uniprot/PDC6I_HUMAN PDC6I_HUMAN] Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (HIV-1 and other lentiviruses). Appears to be an adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis. Involved in HIV-1 virus budding. Can replace TSG101 it its role of supporting HIV-1 release; this function implies the interaction with CHMP4B. May play a role in the regulation of both apoptosis and cell proliferation.<ref>PMID:14505569</ref> <ref>PMID:14505570</ref> <ref>PMID:14739459</ref> <ref>PMID:17853893</ref> <ref>PMID:17428861</ref> <ref>PMID:17556548</ref> |
| - | | + | == Evolutionary Conservation == |
| - | | + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | ==Overview== | + | Check<jmol> |
| - | Retrovirus budding requires short peptide motifs (late domains) located within the viral Gag protein that function by recruiting cellular factors. The YPX(n)L late domains of HIV and other lentiviruses recruit the protein ALIX (also known as AIP1), which also functions in vesicle formation at the multivesicular body and in the abscission stage of cytokinesis. Here, we report the crystal structures of ALIX in complex with the YPX(n)L late domains from HIV-1 and EIAV. The two distinct late domains bind at the same site on the ALIX V domain but adopt different conformations that allow them to make equivalent contacts. Binding studies and functional assays verified the importance of key interface residues and revealed that binding affinities are tuned by context-dependent effects. These results reveal how YPX(n)L late domains recruit ALIX to facilitate virus budding and how ALIX can bind YPX(n)L sequences with both n = 1 and n = 3.
| + | <jmolCheckbox> |
| - | | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r0/2r03_consurf.spt"</scriptWhenChecked> |
| - | ==About this Structure== | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | 2R03 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R03 OCA].
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | | + | </jmolCheckbox> |
| - | ==Reference== | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2r03 ConSurf]. |
| - | Structural and functional studies of ALIX interactions with YPX(n)L late domains of HIV-1 and EIAV., Zhai Q, Fisher RD, Chung HY, Myszka DG, Sundquist WI, Hill CP, Nat Struct Mol Biol. 2008 Jan;15(1):43-9. Epub 2007 Dec 9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18066081 18066081]
| + | <div style="clear:both"></div> |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Protein complex]] | + | [[Category: Large Structures]] |
| - | [[Category: Fisher, R D.]] | + | [[Category: Fisher RD]] |
| - | [[Category: Hill, C P.]] | + | [[Category: Hill CP]] |
| - | [[Category: Zhai, Q.]] | + | [[Category: Zhai Q]] |
| - | [[Category: apoptosis]]
| + | |
| - | [[Category: capsid protein]]
| + | |
| - | [[Category: coiled-coil]]
| + | |
| - | [[Category: core protein]]
| + | |
| - | [[Category: cytoplasm]]
| + | |
| - | [[Category: host-virus interaction]]
| + | |
| - | [[Category: metal-binding]]
| + | |
| - | [[Category: peptide]]
| + | |
| - | [[Category: polymorphism]]
| + | |
| - | [[Category: protein transport]]
| + | |
| - | [[Category: transport]]
| + | |
| - | [[Category: virion]]
| + | |
| - | [[Category: zinc]]
| + | |
| - | [[Category: zinc-finger]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:31:18 2008''
| + | |
| Structural highlights
Function
PDC6I_HUMAN Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (HIV-1 and other lentiviruses). Appears to be an adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis. Involved in HIV-1 virus budding. Can replace TSG101 it its role of supporting HIV-1 release; this function implies the interaction with CHMP4B. May play a role in the regulation of both apoptosis and cell proliferation.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Strack B, Calistri A, Craig S, Popova E, Gottlinger HG. AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding. Cell. 2003 Sep 19;114(6):689-99. PMID:14505569
- ↑ von Schwedler UK, Stuchell M, Muller B, Ward DM, Chung HY, Morita E, Wang HE, Davis T, He GP, Cimbora DM, Scott A, Krausslich HG, Kaplan J, Morham SG, Sundquist WI. The protein network of HIV budding. Cell. 2003 Sep 19;114(6):701-13. PMID:14505570
- ↑ Matsuo H, Chevallier J, Mayran N, Le Blanc I, Ferguson C, Faure J, Blanc NS, Matile S, Dubochet J, Sadoul R, Parton RG, Vilbois F, Gruenberg J. Role of LBPA and Alix in multivesicular liposome formation and endosome organization. Science. 2004 Jan 23;303(5657):531-4. PMID:14739459 doi:10.1126/science.1092425
- ↑ Morita E, Sandrin V, Chung HY, Morham SG, Gygi SP, Rodesch CK, Sundquist WI. Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis. EMBO J. 2007 Oct 3;26(19):4215-27. Epub 2007 Sep 13. PMID:17853893 doi:10.1038/sj.emboj.7601850
- ↑ Usami Y, Popov S, Gottlinger HG. Potent rescue of human immunodeficiency virus type 1 late domain mutants by ALIX/AIP1 depends on its CHMP4 binding site. J Virol. 2007 Jun;81(12):6614-22. Epub 2007 Apr 11. PMID:17428861 doi:10.1128/JVI.00314-07
- ↑ Carlton JG, Martin-Serrano J. Parallels between cytokinesis and retroviral budding: a role for the ESCRT machinery. Science. 2007 Jun 29;316(5833):1908-12. Epub 2007 Jun 7. PMID:17556548 doi:10.1126/science.1143422
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