Proteopedia

3u9g

Crystal structure of the Zinc finger antiviral proteinCrystal structure of the Zinc finger antiviral protein

Structural highlights

3u9g is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.801Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ZCCHV_RAT Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1) and moloney and murine leukemia virus (MoMLV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation.[1] [2] [3] [4] [5] [6] [7]

References

  1. ↑ Gao G, Guo X, Goff SP. Inhibition of retroviral RNA production by ZAP, a CCCH-type zinc finger protein. Science. 2002 Sep 6;297(5587):1703-6. PMID:12215647 doi:http://dx.doi.org/10.1126/science.1074276
  2. ↑ Bick MJ, Carroll JW, Gao G, Goff SP, Rice CM, MacDonald MR. Expression of the zinc-finger antiviral protein inhibits alphavirus replication. J Virol. 2003 Nov;77(21):11555-62. PMID:14557641
  3. ↑ Muller S, Moller P, Bick MJ, Wurr S, Becker S, Gunther S, Kummerer BM. Inhibition of filovirus replication by the zinc finger antiviral protein. J Virol. 2007 Mar;81(5):2391-400. Epub 2006 Dec 20. PMID:17182693 doi:http://dx.doi.org/10.1128/JVI.01601-06
  4. ↑ Guo X, Ma J, Sun J, Gao G. The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):151-6. Epub 2006 Dec 21. PMID:17185417 doi:http://dx.doi.org/10.1073/pnas.0607063104
  5. ↑ MacDonald MR, Machlin ES, Albin OR, Levy DE. The zinc finger antiviral protein acts synergistically with an interferon-induced factor for maximal activity against alphaviruses. J Virol. 2007 Dec;81(24):13509-18. Epub 2007 Oct 10. PMID:17928353 doi:http://dx.doi.org/10.1128/JVI.00402-07
  6. ↑ Kerns JA, Emerman M, Malik HS. Positive selection and increased antiviral activity associated with the PARP-containing isoform of human zinc-finger antiviral protein. PLoS Genet. 2008 Jan;4(1):e21. doi: 10.1371/journal.pgen.0040021. PMID:18225958 doi:http://dx.doi.org/10.1371/journal.pgen.0040021
  7. ↑ Zhu Y, Chen G, Lv F, Wang X, Ji X, Xu Y, Sun J, Wu L, Zheng YT, Gao G. Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15834-9. doi:, 10.1073/pnas.1101676108. Epub 2011 Aug 29. PMID:21876179 doi:http://dx.doi.org/10.1073/pnas.1101676108

3u9g, resolution 1.80Å

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OCA
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