3zhf: Difference between revisions

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New page: '''Unreleased structure''' The entry 3zhf is ON HOLD Authors: Juergens, M.C., Voros, J., Rautureau, G., Shepherd, D., Pye, V.E., Muldoon, J., Johnson, C.M., Ashcroft, A., Freund, S.M.V....
 
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'''Unreleased structure'''


The entry 3zhf is ON HOLD
==gamma 2 adaptin EAR domain crystal structure with preS1 site1 peptide NPDWDFN==
<StructureSection load='3zhf' size='340' side='right'caption='[[3zhf]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zhf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepatitis_B_virus Hepatitis B virus] 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=3ZHF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZHF FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></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=3zhf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zhf OCA], [https://pdbe.org/3zhf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zhf RCSB], [https://www.ebi.ac.uk/pdbsum/3zhf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zhf ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== 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.


Authors: Juergens, M.C., Voros, J., Rautureau, G., Shepherd, D., Pye, V.E., Muldoon, J., Johnson, C.M., Ashcroft, A., Freund, S.M.V., Ferguson, N.
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<ref>PMID:23851574</ref>


Description: gamma 2 adaptin EAR domain crystal structure with preS1 site1 peptide NPDWDFN
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3zhf" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Adaptin 3D structures|Adaptin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Hepatitis B virus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ashcroft A]]
[[Category: Ferguson N]]
[[Category: Freund SMV]]
[[Category: Johnson CM]]
[[Category: Juergens MC]]
[[Category: Muldoon J]]
[[Category: Pye VE]]
[[Category: Rautureau G]]
[[Category: Shepherd D]]
[[Category: Voros J]]

Latest revision as of 14:01, 20 December 2023

gamma 2 adaptin EAR domain crystal structure with preS1 site1 peptide NPDWDFNgamma 2 adaptin EAR domain crystal structure with preS1 site1 peptide NPDWDFN

Structural highlights

3zhf is a 2 chain structure with sequence from Hepatitis B virus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.7Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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

3zhf, resolution 1.70Å

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