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| | ==Crystal structure of the TSG101 UEV domain in complex with FA459 peptide== | | ==Crystal structure of the TSG101 UEV domain in complex with FA459 peptide== |
| - | <StructureSection load='3p9g' size='340' side='right' caption='[[3p9g]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='3p9g' size='340' side='right'caption='[[3p9g]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3p9g]] is a 2 chain structure with sequence 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=3P9G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P9G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3p9g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P9G FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=ZYK:(4R)-4-({[(3,4-DIMETHOXYPHENYL)CARBONYL]AMINO}OXY)-L-PROLINE'>ZYK</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3obq|3obq]], [[3p9h|3p9h]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=ZYK:(4R)-4-({[(3,4-DIMETHOXYPHENYL)CARBONYL]AMINO}OXY)-L-PROLINE'>ZYK</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TSG101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3p9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p9g OCA], [https://pdbe.org/3p9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p9g RCSB], [https://www.ebi.ac.uk/pdbsum/3p9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p9g ProSAT]</span></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=3p9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p9g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p9g RCSB], [http://www.ebi.ac.uk/pdbsum/3p9g PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TS101_HUMAN TS101_HUMAN] Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Involved in the budding of many viruses through an interaction with viral proteins that contain a late-budding motif P-[ST]-A-P. This interaction is essential for viral particle budding of numerous retroviruses.<ref>PMID:11916981</ref> <ref>PMID:17853893</ref> <ref>PMID:17556548</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3p9g" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Gag polyprotein|Gag polyprotein]] | + | *[[Tumor susceptibility gene 101|Tumor susceptibility gene 101]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Hurley, J H]] | + | [[Category: Human immunodeficiency virus 1]] |
| - | [[Category: Im, Y J]] | + | [[Category: Large Structures]] |
| - | [[Category: Protein transport]] | + | [[Category: Hurley JH]] |
| - | [[Category: Ubiquitin]] | + | [[Category: Im YJ]] |
| Structural highlights
Function
TS101_HUMAN Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Involved in the budding of many viruses through an interaction with viral proteins that contain a late-budding motif P-[ST]-A-P. This interaction is essential for viral particle budding of numerous retroviruses.[1] [2] [3]
Publication Abstract from PubMed
Targeting protein-protein interactions is gaining greater recognition as an attractive approach to therapeutic development. An example of this may be found with the human cellular protein encoded by the tumor susceptibility gene 101 (Tsg101), where interaction with the p6 C-terminal domain of the nascent viral Gag protein is required for HIV-1 particle budding and release. This association of Gag with Tsg101 is highly dependent on a "Pro-Thr-Ala-Pro" ("PTAP") peptide sequence within the p6 protein. Although p6-derived peptides offer potential starting points for developing Tsg101-binding inhibitors, the affinities of canonical peptides are outside the useful range (K(d) values greater than 50 muM). Reported herein are crystal structures of Tsg101 in complex with two structurally-modified PTAP-derived peptides. This data define new regions of ligand interaction not previously identified with canonical peptide sequences. This information could be highly useful in the design of Tsg101-binding antagonists.
Elucidation of New Binding Interactions with the Tumor Susceptibility Gene 101 (Tsg101) Protein Using Modified HIV-1 Gag-p6 Derived Peptide Ligands.,Kim SE, Liu F, Im YJ, Stephen AG, Fivash MJ, Waheed AA, Freed EO, Fisher RJ, Hurley JH, Burke TR Jr ACS Med Chem Lett. 2011 May 12;2(5):337-341. PMID:21643473[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bishop N, Horman A, Woodman P. Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates. J Cell Biol. 2002 Apr 1;157(1):91-101. Epub 2002 Mar 26. PMID:11916981 doi:10.1083/jcb.200112080
- ↑ 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
- ↑ 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
- ↑ Kim SE, Liu F, Im YJ, Stephen AG, Fivash MJ, Waheed AA, Freed EO, Fisher RJ, Hurley JH, Burke TR Jr. Elucidation of New Binding Interactions with the Tumor Susceptibility Gene 101 (Tsg101) Protein Using Modified HIV-1 Gag-p6 Derived Peptide Ligands. ACS Med Chem Lett. 2011 May 12;2(5):337-341. PMID:21643473 doi:10.1021/ml1002579
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