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4bcx

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gamma 2 adaptin EAR domain crystal structure

Structural highlights

4bcx is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
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.

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/4bcx"

@@ Line 3: / Line 3: @@
 <StructureSection load='4bcx' size='340' side='right'caption='[[4bcx]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4bcx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BCX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4bcx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BCX FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <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]] 2&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ymt|2ymt]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=PDO:1,3-PROPANDIOL'>PDO</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=4bcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bcx OCA], [https://pdbe.org/4bcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bcx RCSB], [https://www.ebi.ac.uk/pdbsum/4bcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bcx 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>
+[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 ==
@@ Line 26: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Ashcroft, A]]
+[[Category: Ashcroft A]]
-[[Category: Ferguson, N]]
+[[Category: Ferguson N]]
-[[Category: Freund, S M.V]]
+[[Category: Freund SMV]]
-[[Category: Johnson, C M]]
+[[Category: Johnson CM]]
-[[Category: Juergens, M C]]
+[[Category: Juergens MC]]
-[[Category: Muldoon, J]]
+[[Category: Muldoon J]]
-[[Category: Pye, V E]]
+[[Category: Pye VE]]
-[[Category: Rautureau, G]]
+[[Category: Rautureau G]]
-[[Category: Shepherd, D]]
+[[Category: Shepherd D]]
-[[Category: Voros, J]]
+[[Category: Voros J]]
-[[Category: Gae]]
-[[Category: Gamma adaptin]]
-[[Category: Protein transport]]

4bcx

From Proteopedia

Current revision

gamma 2 adaptin EAR domain crystal structure

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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