PDBsum entry 2ymt

Protein transport

PDB id: 2ymt

Contents

Protein chain

122 a.a.

Ligands

GLU-TRP-GLY-PRO-TRP-VAL-NH2

PDO

Waters ×125

PDB id:

2ymt

Name:

Protein transport

Title:

Gamma 2 adaptin ear domain crystal structure with phage peptide geewgpwv

Structure:

Ap-1 complex subunit gamma-like 2. Chain: a. Fragment: ear domain, residues 665-785. Synonym: gamma2-adaptin, g2ad, gamma 2 adaptin ear domain. Engineered: yes. Phage display derived gamma 2 adaptin ear domain binding peptide. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: c41. Synthetic: yes. Synthetic construct. Organism_taxid: 32630

Resolution:

1.80Å R-factor: 0.188 R-free: 0.242

Authors:

M.C.Juergens,J.Voros,G.Rautureau,D.Shepherd,V.E.Pye,J.Muldoon, C.M.Johnson,A.Ashcroft,S.M.V.Freund,N.Ferguson

Key ref:

M.C.Jürgens et al. (2013). The hepatitis B virus preS1 domain hijacks host trafficking proteins by motif mimicry. Nat Chem Biol, 9, 540-547. PubMed id: 23851574 DOI: 10.1038/nchembio.1294

Date:

10-Oct-12 Release date: 10-Jul-13

Protein chain

O75843  (AP1G2_HUMAN) -  AP-1 complex subunit gamma-like 2 from Homo sapiens

Seq: 785 a.a.

Struc: 122 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1038/nchembio.1294

Nat Chem Biol 9:540-547 (2013)

PubMed id: 23851574

The hepatitis B virus preS1 domain hijacks host trafficking proteins by motif mimicry.

M.C.Jürgens, J.Vörös, G.J.Rautureau, D.A.Shepherd, V.E.Pye, J.Muldoon, C.M.Johnson, A.E.Ashcroft, S.M.Freund, N.Ferguson.

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.