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3zhf

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Revision as of 12:33, 1 July 2015

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

Structural highlights

3zhf is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:	,
Resources:	FirstGlance, OCA, RCSB, PDBsum

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] [Q67953_HBV] The middle envelope protein plays an important role in the budding of the virion. It is involved in the induction of budding in a nucleocapsid independent way. In this process the majority of envelope proteins bud to form subviral lipoprotein particles of 22 nm of diameter that do not contain a nucleocapsid (By similarity).[SAAS:SAAS000349_004_055156]

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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3zhf"

@@ Line 2: / Line 2: @@
 <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 [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZHF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3zhf]] 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=3ZHF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZHF FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></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></td></tr>
@@ Line 24: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Ashcroft, A]]
 [[Category: Ferguson, N]]

3zhf

From Proteopedia

Revision as of 12:33, 1 July 2015

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

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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