4u2x

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

Structural highlights

4u2x is a 6 chain structure with sequence from Ebola virus - Mayinga, Zaire, 1976 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.153Å
Ligands:CL
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VP24_EBOZM Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways. Blocks the IFN-induced nuclear accumulation of host phosphorylated STAT1, by interacting with the STAT1-binding region of host importin alpha-1/KPNA1 protein, thereby inhibiting the latter. Without the activity of this protein, activated STAT1 would not enter the nucleus and be unable to activate IFN-induced genes. Plays a role in assembly of viral nucleocapsid and virion budding. May act as a minor matrix protein that plays a role in assembly of viral nucleocapsid and virion budding.[1] [2] [3] [4]

Publication Abstract from PubMed

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.

Ebola Virus VP24 Targets a Unique NLS Binding Site on Karyopherin Alpha 5 to Selectively Compete with Nuclear Import of Phosphorylated STAT1.,Xu W, Edwards MR, Borek DM, Feagins AR, Mittal A, Alinger JB, Berry KN, Yen B, Hamilton J, Brett TJ, Pappu RV, Leung DW, Basler CF, Amarasinghe GK Cell Host Microbe. 2014 Aug 13;16(2):187-200. doi: 10.1016/j.chom.2014.07.008. PMID:25121748[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
51 reviews cite this structure
Ten Strategies of Interferon Evasion by Viruses.
García-Sastre et al. (2017)
50 more
77 other articles
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See Also

References

  1. ↑ Huang Y, Xu L, Sun Y, Nabel GJ. The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein. Mol Cell. 2002 Aug;10(2):307-16. PMID:12191476
  2. ↑ Han Z, Boshra H, Sunyer JO, Zwiers SH, Paragas J, Harty RN. Biochemical and functional characterization of the Ebola virus VP24 protein: implications for a role in virus assembly and budding. J Virol. 2003 Feb;77(3):1793-800. PMID:12525613
  3. ↑ Licata JM, Johnson RF, Han Z, Harty RN. Contribution of ebola virus glycoprotein, nucleoprotein, and VP24 to budding of VP40 virus-like particles. J Virol. 2004 Jul;78(14):7344-51. PMID:15220407 doi:http://dx.doi.org/10.1128/JVI.78.14.7344-7351.2004
  4. ↑ Reid SP, Valmas C, Martinez O, Sanchez FM, Basler CF. Ebola virus VP24 proteins inhibit the interaction of NPI-1 subfamily karyopherin alpha proteins with activated STAT1. J Virol. 2007 Dec;81(24):13469-77. Epub 2007 Oct 10. PMID:17928350 doi:http://dx.doi.org/10.1128/JVI.01097-07
  5. ↑ Xu W, Edwards MR, Borek DM, Feagins AR, Mittal A, Alinger JB, Berry KN, Yen B, Hamilton J, Brett TJ, Pappu RV, Leung DW, Basler CF, Amarasinghe GK. 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. 2014 Aug 13;16(2):187-200. doi: 10.1016/j.chom.2014.07.008. PMID:25121748 doi:http://dx.doi.org/10.1016/j.chom.2014.07.008

Contents


PDB ID 4u2x

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OCA

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