6e5u

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Crystal structure of the mRNA export receptor NXF1/NXT1 in complex with influenza virus NS1 proteinCrystal structure of the mRNA export receptor NXF1/NXT1 in complex with influenza virus NS1 protein

Structural highlights

6e5u is a 16 chain structure with sequence from Homo sapiens and Influenza A virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.8Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NXF1_HUMAN Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm. The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5.[1] [2]

Publication Abstract from PubMed

Influenza viruses antagonize key immune defence mechanisms via the virulence factor non-structural protein 1 (NS1). A key mechanism of virulence by NS1 is blocking nuclear export of host messenger RNAs, including those encoding immune factors(1-3); however, the direct cellular target of NS1 and the mechanism of host mRNA export inhibition are not known. Here, we identify the target of NS1 as the mRNA export receptor complex, nuclear RNA export factor 1-nuclear transport factor 2-related export protein 1 (NXF1-NXT1), which is the principal receptor mediating docking and translocation of mRNAs through the nuclear pore complex via interactions with nucleoporins(4,5). We determined the crystal structure of NS1 in complex with NXF1-NXT1 at 3.8 A resolution. The structure reveals that NS1 prevents binding of NXF1-NXT1 to nucleoporins, thereby inhibiting mRNA export through the nuclear pore complex into the cytoplasm for translation. We demonstrate that a mutant influenza virus deficient in binding NXF1-NXT1 does not block host mRNA export and is attenuated. This attenuation is marked by the release of mRNAs encoding immune factors from the nucleus. In sum, our study uncovers the molecular basis of a major nuclear function of influenza NS1 protein that causes potent blockage of host gene expression and contributes to inhibition of host immunity.

Structural basis for influenza virus NS1 protein block of mRNA nuclear export.,Zhang K, Xie Y, Munoz-Moreno R, Wang J, Zhang L, Esparza M, Garcia-Sastre A, Fontoura BMA, Ren Y Nat Microbiol. 2019 Oct;4(10):1671-1679. doi: 10.1038/s41564-019-0482-x. Epub, 2019 Jul 1. PMID:31263181[3]

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

See Also

References

  1. Gruter P, Tabernero C, von Kobbe C, Schmitt C, Saavedra C, Bachi A, Wilm M, Felber BK, Izaurralde E. TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus. Mol Cell. 1998 Apr;1(5):649-59. PMID:9660949
  2. Katahira J, Inoue H, Hurt E, Yoneda Y. Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export of HSP70 mRNA. EMBO J. 2009 Mar 4;28(5):556-67. doi: 10.1038/emboj.2009.5. Epub 2009 Jan 22. PMID:19165146 doi:10.1038/emboj.2009.5
  3. Zhang K, Xie Y, Munoz-Moreno R, Wang J, Zhang L, Esparza M, Garcia-Sastre A, Fontoura BMA, Ren Y. Structural basis for influenza virus NS1 protein block of mRNA nuclear export. Nat Microbiol. 2019 Oct;4(10):1671-1679. doi: 10.1038/s41564-019-0482-x. Epub, 2019 Jul 1. PMID:31263181 doi:http://dx.doi.org/10.1038/s41564-019-0482-x

6e5u, resolution 3.80Å

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