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X-ray structure of influenza virus NS1 effector domain

Abstract

The nonstructural protein NS1 of influenza virus is an antagonist of host immune responses and is implicated in virulence. It has two domains, an N-terminal double-stranded RNA–binding domain (RBD) and an effector domain crucial for RBD function, for nuclear export and for sequestering messenger RNA–processing proteins. Here we present the crystallographic structure of the effector domain, which has a novel fold and suggests mechanisms for increased virulence in H5N1 strains.

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Figure 1: NS1 effector domain structure.
Figure 2: The effector domain dimer and the structurally dynamic cleft.

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Acknowledgements

We thank P. Palese (Mt. Sinai School of Medicine) for the NS1 clone and P. Wyde for helpful discussions. We acknowledge support from the US National Institutes of Health (AI36040) and the Welch Foundation to B.V.V.P. and from a US National Institutes of Health virology training grant (AI07471) to Z.A.B. We thank H. Bellamy and the staff at the Center for Advanced Microstructures & Devices, as well as the staff of beamline SBC-CAT 19ID at the Advanced Photon Source (supported by the US Department of Energy, Basic Energy Sciences, Office of Science), for their help during data collection.

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Correspondence to B V Venkataram Prasad.

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Supplementary information

Supplementary Fig. 1

Size-exclusion chromatography of NS1ΔN73 (PDF 86 kb)

Supplementary Fig. 2

Topology diagram of the monomer. (PDF 123 kb)

Supplementary Fig. 3

Model for the orientation of the RBD in the NS1 protein (PDF 138 kb)

Supplementary Table 1

Data collection and model refinement statistics (PDF 83 kb)

Supplementary Methods (PDF 97 kb)

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Bornholdt, Z., Prasad, B. X-ray structure of influenza virus NS1 effector domain. Nat Struct Mol Biol 13, 559–560 (2006). https://doi.org/10.1038/nsmb1099

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