Washington U in St. Louis2014-09-18 3:30 PM

Ebola Virus VP24 Targets a Unique NLS Binding Site on Karyopherin Alpha 5 to Selectively Compete with Nuclear Import of Phosphorylated STAT1

Highlights

•Structure of Ebola virus VP24 bound to the C terminus of karyopherin alpha 5 (KPNA5)

•VP24 binds a unique nonclassical NLS binding site in KPNA5

•VP24 and phosphorylated STAT1 share a common binding site on KPNA5 binding

•VP24 competes with nuclear import of phosphorylated STAT1 to counter STAT signaling


Summary

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.


Full Article 

KEYWORDS

SHARE & LIKE

COMMENTS

ABOUT THE AUTHOR

Washington U in St. Louis

0 Following 0 Fans 0 Projects 9 Articles

SIMILAR ARTICLES

AbstractNon-sedentary work configurations, which encourage standing rather than sitting in the course of work, are becoming increasingly prevalent in o

Read More

SignificanceThe assessment of the paleobiology and morphological affinities of the Neandertals and other Late Pleistocene archaic humans is central to

Read More

Highlights•Individuals with severe episodic amnesia, e.g., KC, retain many kinds of temporal consciousness.•KC and others with episodic amnesia grasp t

Read More

AbstractImportance  Although autism spectrum disorder (ASD) is known to be heritable, patterns of inheritance of subclinical autistic traits in nonclin

Read More

AbstractThe parallel evolution of increased sensorimotor intelligence in humans and capuchins has been linked to the cognitive and manual demands of se

Read More

AbstractA current controversy is whether patients with sepsis progress to an immunosuppressed state. We hypothesized that reactivation of latent viruse

Read More

AbstractThe Federal Reserve injected unprecedented liquidity into banks during the crisis using the discount window and Term Auction Facility. We exami

Read More

Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth re

Read More

Highlights•Structure of Ebola virus VP24 bound to the C terminus of karyopherin alpha 5 (KPNA5)•VP24 binds a unique nonclassical NLS binding site in KP

Read More