3zhf | pdb_00003zhf

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

spinqualitylabelsall models 3zhf, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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: EDO, PEG NonStd Res: ACE, NH2 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). [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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adaptin

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