PDBsum entry 4m0q

Viral protein

PDB id: 4m0q

Contents

Protein chains

222 a.a.

Waters ×170

PDB id:

4m0q

Name:

Viral protein

Title:

Ebola virus vp24 structure

Structure:

Membrane-associated protein vp24. Chain: a, b. Fragment: unp residues 11-231. Engineered: yes

Source:

Zaire ebolavirus. Zebov. Organism_taxid: 186538. Gene: vp24. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.92Å R-factor: 0.211 R-free: 0.232

Authors:

W.Xu,D.W.Leung,D.Borek,G.K.Amarasinghe

Key ref:

M.R.Edwards et al. (2014). The Marburg virus VP24 protein interacts with Keap1 to activate the cytoprotective antioxidant response pathway. Cell Rep, 6, 1017-1025. PubMed id: 24630991 DOI: 10.1016/j.celrep.2014.01.043

Date:

01-Aug-13 Release date: 19-Mar-14

Protein chains

Q05322  (VP24_EBOZM) -  Membrane-associated protein VP24 from Zaire ebolavirus (strain Mayinga-76)

Seq: 251 a.a.

Struc: 222 a.a.*

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

DOI no: 10.1016/j.celrep.2014.01.043

Cell Rep 6:1017-1025 (2014)

PubMed id: 24630991

The Marburg virus VP24 protein interacts with Keap1 to activate the cytoprotective antioxidant response pathway.

M.R.Edwards, B.Johnson, C.E.Mire, W.Xu, R.S.Shabman, L.N.Speller, D.W.Leung, T.W.Geisbert, G.K.Amarasinghe, C.F.Basler.

ABSTRACT

Kelch-like ECH-associated protein 1 (Keap1) is a ubiquitin E3 ligase specificity factor that targets transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) for ubiquitination and degradation. Disrupting Keap1-Nrf2 interaction stabilizes Nrf2, resulting in Nrf2 nuclear accumulation, binding to antioxidant response elements (AREs), and transcription of cytoprotective genes. Marburg virus (MARV) is a zoonotic pathogen that likely uses bats as reservoir hosts. We demonstrate that MARV protein VP24 (mVP24) binds the Kelch domain of either human or bat Keap1. This binding is of high affinity and 1:1 stoichiometry and activates Nrf2. Modeling based on the Zaire ebolavirus (EBOV) VP24 (eVP24) structure identified in mVP24 an acidic loop (K-loop) critical for Keap1 interaction. Transfer of the K-loop to eVP24, which otherwise does not bind Keap1, confers Keap1 binding and Nrf2 activation, and infection by MARV, but not EBOV, activates ARE gene expression. Therefore, MARV targets Keap1 to activate Nrf2-induced cytoprotective responses during infection.