4BCX

gamma 2 adaptin EAR domain crystal structure

4BCX の概要

• エントリーDOI: 10.2210/pdb4bcx/pdb
• 関連するPDBエントリー: 2YMT
• 分子名称: AP-1 COMPLEX SUBUNIT GAMMA-LIKE 2, IMIDAZOLE, 1,3-PROPANDIOL, ... (4 entities in total)
• 機能のキーワード: protein transport, gae, gamma adaptin
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Golgi apparatus membrane ; Peripheral membrane protein; Cytoplasmic side : O75843
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13907.92

構造登録者

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. (登録日: 2012-10-03, 公開日: 2013-07-10, 最終更新日: 2023-12-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)