4U2X

Ebola virus VP24 in complex with Karyopherin alpha 5 C-terminus

Summary for 4U2X

• Entry DOI: 10.2210/pdb4u2x/pdb
• Descriptor: Membrane-associated protein VP24, Importin subunit alpha-6, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: evp24, importin alpha6, immune antagonist, viral protein
• Biological source: Zaire ebolavirus (ZEBOV); More
• Total number of polymer chains: 6
• Total formula weight: 131767.07

Authors

Xu, W.,Leung, D.,Borek, D.,Amarasinghe, G. (deposition date: 2014-07-18, release date: 2014-08-13, Last modification date: 2024-10-30)

Primary citation

Xu, W.,Edwards, M.R.,Borek, D.M.,Feagins, A.R.,Mittal, A.,Alinger, J.B.,Berry, K.N.,Yen, B.,Hamilton, J.,Brett, T.J.,Pappu, R.V.,Leung, D.W.,Basler, C.F.,Amarasinghe, G.K.
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, 2014

PubMed 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.

PubMed: 25121748
DOI: 10.1016/j.chom.2014.07.008

Experimental method

X-RAY DIFFRACTION (3.153 Å)