PDBsum entry 4u2x

Viral protein

PDB id: 4u2x

Contents

Protein chains

216 a.a.

170 a.a.

Metals

_CL ×2

Waters ×24

PDB id:

4u2x

Name:

Viral protein

Title:

Ebola virus vp24 in complex with karyopherin alpha 5 c-terminus

Structure:

Membrane-associated protein vp24. Chain: a, b, c. Fragment: evp24. Engineered: yes. Importin subunit alpha-6. Chain: d, e, f. Fragment: kpna5. Synonym: karyopherin subunit alpha-5. Engineered: yes

Source:

Zaire ebolavirus. Zebov. Organism_taxid: 128952. Strain: mayinga-76. Gene: vp24. Expressed in: escherichia coli. Expression_system_taxid: 469008. Homo sapiens. Human.

Resolution:

3.15Å R-factor: 0.216 R-free: 0.249

Authors:

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

Key ref:

W.Xu et al. (2014). Ebola virus VP24 targets a unique NLS binding site on karyopherin alpha 5 to selectively compete with nuclear import of phosphorylated STAT1. Cell Host Microbe, 16, 187-200. PubMed id: 25121748 DOI: 10.1016/j.chom.2014.07.008

Date:

18-Jul-14 Release date: 13-Aug-14

Protein chains

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

Seq: 251 a.a.

Struc: 216 a.a.

Protein chains

O15131  (IMA6_HUMAN) -  Importin subunit alpha-6 from Homo sapiens

Seq: 539 a.a.

Struc: 170 a.a.

DOI no: 10.1016/j.chom.2014.07.008

Cell Host Microbe 16:187-200 (2014)

PubMed id: 25121748

Ebola virus VP24 targets a unique NLS binding site on karyopherin alpha 5 to selectively compete with nuclear import of phosphorylated STAT1.

W.Xu, M.R.Edwards, D.M.Borek, A.R.Feagins, A.Mittal, J.B.Alinger, K.N.Berry, B.Yen, J.Hamilton, T.J.Brett, R.V.Pappu, D.W.Leung, C.F.Basler, G.K.Amarasinghe.

ABSTRACT

During antiviral defense, interferon (IFN) signaling triggers nuclear transport of tyrosine-phosphorylated STAT1 (PY-STAT1), which occurs via a subset of karyopherin alpha (KPNA) nuclear transporters. Many viruses, including Ebola virus, actively antagonize STAT1 signaling to counteract the antiviral effects of IFN. Ebola virus VP24 protein (eVP24) binds KPNA to inhibit PY-STAT1 nuclear transport and render cells refractory to IFNs. We describe the structure of human KPNA5 C terminus in complex with eVP24. In the complex, eVP24 recognizes a unique nonclassical nuclear localization signal (NLS) binding site on KPNA5 that is necessary for efficient PY-STAT1 nuclear transport. eVP24 binds KPNA5 with very high affinity to effectively compete with and inhibit PY-STAT1 nuclear transport. In contrast, eVP24 binding does not affect the transport of classical NLS cargo. Thus, eVP24 counters cell-intrinsic innate immunity by selectively targeting PY-STAT1 nuclear import while leaving the transport of other cargo that may be required for viral replication unaffected.