2YMT

gamma 2 adaptin EAR domain crystal structure with phage peptide GEEWGPWV

Summary for 2YMT

• Entry DOI: 10.2210/pdb2ymt/pdb
• Related: 4BCX
• Descriptor: AP-1 COMPLEX SUBUNIT GAMMA-LIKE 2, PHAGE DISPLAY DERIVED GAMMA 2 ADAPTIN EAR DOMAIN BINDING PEPTIDE, 1,3-PROPANDIOL, ... (4 entities in total)
• Functional Keywords: protein transport
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Golgi apparatus membrane ; Peripheral membrane protein; Cytoplasmic side : O75843
• Total number of polymer chains: 2
• Total formula weight: 14795.86

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. (deposition date: 2012-10-10, release date: 2013-07-10, Last modification date: 2023-12-20)

Primary citation

Jurgens, M.C.,Voros, J.,Rautureau, G.J.P.,Shepherd, D.A.,Pye, V.E.,Muldoon, J.,Johnson, C.M.,Ashcroft, A.E.,Freund, S.M.V.,Ferguson, N.
The Hepatitis B Virus Pres1 Domain Hijacks Host Trafficking Proteins by Motif Mimicry.
Nat.Chem.Biol., 9:540-, 2013

PubMed Abstract: 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, γ2-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 γ2-adaptin. NMR, protein engineering, X-ray crystallography and MS showed that preS1 contains multiple γ2-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-γ2-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 γ2-EAR-preS1 interaction.

PubMed: 23851574
DOI: 10.1038/NCHEMBIO.1294

Experimental method

X-RAY DIFFRACTION (1.802 Å)