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| | ==gamma 2 adaptin EAR domain crystal structure with phage peptide GEEWGPWV== | | ==gamma 2 adaptin EAR domain crystal structure with phage peptide GEEWGPWV== |
| - | <StructureSection load='2ymt' size='340' side='right' caption='[[2ymt]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='2ymt' size='340' side='right'caption='[[2ymt]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ymt]] is a 2 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=2YMT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YMT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ymt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YMT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YMT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PDO:1,3-PROPANDIOL'>PDO</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]] 1.802Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PDO:1,3-PROPANDIOL'>PDO</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bcx|4bcx]]</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=2ymt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ymt OCA], [https://pdbe.org/2ymt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ymt RCSB], [https://www.ebi.ac.uk/pdbsum/2ymt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ymt 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=2ymt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ymt OCA], [http://pdbe.org/2ymt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ymt RCSB], [http://www.ebi.ac.uk/pdbsum/2ymt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ymt ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AP1G2_HUMAN AP1G2_HUMAN]] May function in protein sorting in late endosomes or multivesucular bodies (MVBs). Involved in MVB-assisted maturation of hepatitis B virus (HBV).<ref>PMID:9733768</ref> <ref>PMID:16867982</ref> <ref>PMID:17553870</ref> | + | [https://www.uniprot.org/uniprot/AP1G2_HUMAN AP1G2_HUMAN] May function in protein sorting in late endosomes or multivesucular bodies (MVBs). Involved in MVB-assisted maturation of hepatitis B virus (HBV).<ref>PMID:9733768</ref> <ref>PMID:16867982</ref> <ref>PMID:17553870</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Adaptin|Adaptin]] | + | *[[Adaptin 3D structures|Adaptin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Ashcroft, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Ferguson, N]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Freund, S M.V]] | + | [[Category: Ashcroft A]] |
| - | [[Category: Johnson, C M]] | + | [[Category: Ferguson N]] |
| - | [[Category: Juergens, M C]] | + | [[Category: Freund SMV]] |
| - | [[Category: Muldoon, J]] | + | [[Category: Johnson CM]] |
| - | [[Category: Pye, V E]] | + | [[Category: Juergens MC]] |
| - | [[Category: Rautureau, G]] | + | [[Category: Muldoon J]] |
| - | [[Category: Shepherd, D]] | + | [[Category: Pye VE]] |
| - | [[Category: Voros, J]] | + | [[Category: Rautureau G]] |
| - | [[Category: Protein transport]]
| + | [[Category: Shepherd D]] |
| | + | [[Category: Voros J]] |
| Structural highlights
Function
AP1G2_HUMAN May function in protein sorting in late endosomes or multivesucular bodies (MVBs). Involved in MVB-assisted maturation of hepatitis B virus (HBV).[1] [2] [3]
Publication Abstract from PubMed
Hepatitis B virus (HBV) is an infectious, potentially lethal human pathogen. However, there are no effective therapies for chronic HBV infections. Antiviral development is hampered by the lack of high-resolution structures for essential HBV protein-protein interactions. The interaction between preS1, an HBV surface-protein domain, and its human binding partner, gamma2-adaptin, subverts the membrane-trafficking apparatus to mediate virion export. This interaction is a putative drug target. We report here atomic-resolution descriptions of the binding thermodynamics and structural biology of the interaction between preS1 and the EAR domain of gamma2-adaptin. NMR, protein engineering, X-ray crystallography and MS showed that preS1 contains multiple gamma2-EAR-binding motifs that mimic the membrane-trafficking motifs (and binding modes) of host proteins. These motifs localize together to a relatively rigid, functionally important region of preS1, an intrinsically disordered protein. The preS1-gamma2-EAR interaction was relatively weak and efficiently outcompeted by a synthetic peptide. Our data provide the structural road map for developing peptidomimetic antivirals targeting the gamma2-EAR-preS1 interaction.
The hepatitis B virus preS1 domain hijacks host trafficking proteins by motif mimicry.,Jurgens MC, Voros J, Rautureau GJ, Shepherd DA, Pye VE, Muldoon J, Johnson CM, Ashcroft AE, Freund SM, Ferguson N Nat Chem Biol. 2013 Jul 14. doi: 10.1038/nchembio.1294. PMID:23851574[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Takatsu H, Sakurai M, Shin HW, Murakami K, Nakayama K. Identification and characterization of novel clathrin adaptor-related proteins. J Biol Chem. 1998 Sep 18;273(38):24693-700. PMID:9733768
- ↑ Rost M, Mann S, Lambert C, Doring T, Thome N, Prange R. Gamma-adaptin, a novel ubiquitin-interacting adaptor, and Nedd4 ubiquitin ligase control hepatitis B virus maturation. J Biol Chem. 2006 Sep 29;281(39):29297-308. Epub 2006 Jul 25. PMID:16867982 doi:M603517200
- ↑ Lambert C, Doring T, Prange R. Hepatitis B virus maturation is sensitive to functional inhibition of ESCRT-III, Vps4, and gamma 2-adaptin. J Virol. 2007 Sep;81(17):9050-60. Epub 2007 Jun 6. PMID:17553870 doi:JVI.00479-07
- ↑ Jurgens MC, Voros J, Rautureau GJ, Shepherd DA, Pye VE, Muldoon J, Johnson CM, Ashcroft AE, Freund SM, Ferguson N. The hepatitis B virus preS1 domain hijacks host trafficking proteins by motif mimicry. Nat Chem Biol. 2013 Jul 14. doi: 10.1038/nchembio.1294. PMID:23851574 doi:10.1038/nchembio.1294
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