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PDBsum entry 2rhk
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Viral protein/nuclear protein PDB id
2rhk

 

 

 

 

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Contents
Protein chains
119 a.a.
63 a.a. *
60 a.a. *
Ligands
NO3 ×5
TRS
Metals
_ZN ×4
Waters ×185
* Residue conservation analysis
PDB id:
2rhk
Name: Viral protein/nuclear protein
Title: Crystal structure of influenza a ns1a protein in complex with f2f3 fragment of human cellular factor cpsf30, northeast structural genomics targets or8c and hr6309a
Structure: Non-structural protein 1. Chain: a, b. Fragment: ns1a effector domain (unp residues 85-215). Synonym: ns1, ns1a. Engineered: yes. Cleavage and polyadenylation specificity factor subunit 4. Chain: c, d. Fragment: f2f3 zinc-binding domains (unp residues 61-121). Synonym: cleavage and polyadenylation specificity factor 30 kda
Source: Influenza a virus. Organism_taxid: 11320. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.
Resolution:
1.95Å     R-factor:   0.210     R-free:   0.234
Authors: K.Das,L.-C.Ma,R.Xiao,B.Radvansky,J.Aramini,L.Zhao,E.Arnold,R.M.Krug, G.T.Montelione,Northeast Structural Genomics Consortium (Nesg)
Key ref: K.Das et al. (2008). Structural basis for suppression of a host antiviral response by influenza A virus. Proc Natl Acad Sci U S A, 105, 13093-13098. PubMed id: 18725644
Date:
09-Oct-07     Release date:   01-Jul-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
P03495  (NS1_I72A2) -  Non-structural protein 1 from Influenza A virus (strain A/Udorn/307/1972 H3N2)
Seq:
Struc: 		237 a.a.
119 a.a.
Protein chain
O95639  (CPSF4_HUMAN) -  Cleavage and polyadenylation specificity factor subunit 4 from Homo sapiens
Seq:
Struc: 		269 a.a.
63 a.a.*
Protein chain
O95639  (CPSF4_HUMAN) -  Cleavage and polyadenylation specificity factor subunit 4 from Homo sapiens
Seq:
Struc: 		269 a.a.
60 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 8 residue positions (black crosses)

 

 
Proc Natl Acad Sci U S A 105:13093-13098 (2008)
PubMed id: 18725644  
 
 
Structural basis for suppression of a host antiviral response by influenza A virus.
K.Das, L.C.Ma, R.Xiao, B.Radvansky, J.Aramini, L.Zhao, J.Marklund, R.L.Kuo, K.Y.Twu, E.Arnold, R.M.Krug, G.T.Montelione.
 
  ABSTRACT  
 
Influenza A viruses are responsible for seasonal epidemics and high mortality pandemics. A major function of the viral NS1A protein, a virulence factor, is the inhibition of the production of IFN-beta mRNA and other antiviral mRNAs. The NS1A protein of the human influenza A/Udorn/72 (Ud) virus inhibits the production of these antiviral mRNAs by binding the cellular 30-kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), which is required for the 3' end processing of all cellular pre-mRNAs. Here we report the 1.95-A resolution X-ray crystal structure of the complex formed between the second and third zinc finger domain (F2F3) of CPSF30 and the C-terminal domain of the Ud NS1A protein. The complex is a tetramer, in which each of two F2F3 molecules wraps around two NS1A effector domains that interact with each other head-to-head. This structure identifies a CPSF30 binding pocket on NS1A comprised of amino acid residues that are highly conserved among human influenza A viruses. Single amino acid changes within this binding pocket eliminate CPSF30 binding, and a recombinant Ud virus expressing an NS1A protein with such a substitution is attenuated and does not inhibit IFN-beta pre-mRNA processing. This binding pocket is a potential target for antiviral drug development. The crystal structure also reveals that two amino acids outside of this pocket, F103 and M106, which are highly conserved (>99%) among influenza A viruses isolated from humans, participate in key hydrophobic interactions with F2F3 that stabilize the complex.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
22419161 I.Marazzi, J.S.Ho, J.Kim, B.Manicassamy, S.Dewell, R.A.Albrecht, C.W.Seibert, U.Schaefer, K.L.Jeffrey, R.K.Prinjha, K.Lee, A.García-Sastre, R.G.Roeder, and A.Tarakhovsky (2012).
Suppression of the antiviral response by an influenza histone mimic.
  Nature, 483, 428-433.  
21464929 P.S.Kerry, J.Ayllon, M.A.Taylor, C.Hass, A.Lewis, A.García-Sastre, R.E.Randall, B.G.Hale, and R.J.Russell (2011).
A transient homotypic interaction model for the influenza A virus NS1 protein effector domain.
  PLoS One, 6, e17946.
PDB codes: 3o9q 3o9r 3o9s 3o9t 3o9u 3oa9
21295486 Q.Yang, M.Coseno, G.M.Gilmartin, and S.Doublié (2011).
Crystal structure of a human cleavage factor CFI(m)25/CFI(m)68/RNA complex provides an insight into poly(A) site recognition and RNA looping.
  Structure, 19, 368-377.
PDB codes: 3q2s 3q2t
20721688 A.Panshin, N.Golender, I.Davidson, S.Nagar, M.Garsia, M.W.Jackwood, E.Mundt, A.Alturi, and S.Perk (2010).
Variability of NS1 proteins among H9N2 avian influenza viruses isolated in Israel during 2000-2009.
  Virus Genes, 41, 396-405.  
20444891 B.G.Hale, J.Steel, R.A.Medina, B.Manicassamy, J.Ye, D.Hickman, R.Hai, M.Schmolke, A.C.Lowen, D.R.Perez, and A.García-Sastre (2010).
Inefficient control of host gene expression by the 2009 pandemic H1N1 influenza A virus NS1 protein.
  J Virol, 84, 6909-6922.  
20133840 B.G.Hale, P.S.Kerry, D.Jackson, B.L.Precious, A.Gray, M.J.Killip, R.E.Randall, and R.J.Russell (2010).
Structural insights into phosphoinositide 3-kinase activation by the influenza A virus NS1 protein.
  Proc Natl Acad Sci U S A, 107, 1954-1959.
PDB code: 3l4q
20020828 B.G.Hale, R.A.Albrecht, and A.García-Sastre (2010).
Innate immune evasion strategies of influenza viruses.
  Future Microbiol, 5, 23-41.  
20826615 H.Han, Z.Q.Cui, W.Wang, Z.P.Zhang, H.P.Wei, Y.F.Zhou, and X.E.Zhang (2010).
New regulatory mechanisms for the intracellular localization and trafficking of influenza A virus NS1 protein revealed by comparative analysis of A/PR/8/34 and A/Sydney/5/97.
  J Gen Virol, 91, 2907-2917.  
20383144 K.Das, J.M.Aramini, L.C.Ma, R.M.Krug, and E.Arnold (2010).
Structures of influenza A proteins and insights into antiviral drug targets.
  Nat Struct Mol Biol, 17, 530-538.  
20519456 N.C.Robb, D.Jackson, F.T.Vreede, and E.Fodor (2010).
Splicing of influenza A virus NS1 mRNA is independent of the viral NS1 protein.
  J Gen Virol, 91, 2331-2340.  
19995550 S.Xia, and J.D.Robertus (2010).
X-ray structures of NS1 effector domain mutants.
  Arch Biochem Biophys, 494, 198-204.
PDB codes: 3kwg 3kwi
20007264 W.Ma, D.Brenner, Z.Wang, B.Dauber, C.Ehrhardt, K.Högner, S.Herold, S.Ludwig, T.Wolff, K.Yu, J.A.Richt, O.Planz, and S.Pleschka (2010).
The NS segment of an H5N1 highly pathogenic avian influenza virus (HPAIV) is sufficient to alter replication efficiency, cell tropism, and host range of an H7N1 HPAIV.
  J Virol, 84, 2122-2133.  
20463066 Y.Li, X.Lu, J.Li, N.Bérubé, K.L.Giest, Q.Liu, D.H.Anderson, and Y.Zhou (2010).
Genetically engineered, biarsenically labeled influenza virus allows visualization of viral NS1 protein in living cells.
  J Virol, 84, 7204-7213.  
19726611 G.Kochs, L.Martínez-Sobrido, S.Lienenklaus, S.Weiss, A.García-Sastre, and P.Staeheli (2009).
Strong interferon-inducing capacity of a highly virulent variant of influenza A virus strain PR8 with deletions in the NS1 gene.
  J Gen Virol, 90, 2990-2994.  
19052083 R.L.Kuo, and R.M.Krug (2009).
Influenza a virus polymerase is an integral component of the CPSF30-NS1A protein complex in infected cells.
  J Virol, 83, 1611-1616.  
19428126 R.M.Krug, and J.M.Aramini (2009).
Emerging antiviral targets for influenza A virus.
  Trends Pharmacol Sci, 30, 269-277.  
19203576 R.Salomon, and R.G.Webster (2009).
The influenza virus enigma.
  Cell, 136, 402-410.  
19708812 T.Wolff, and S.Ludwig (2009).
Influenza viruses control the vertebrate type I interferon system: factors, mechanisms, and consequences.
  J Interferon Cytokine Res, 29, 549-557.  
19471867 Y.Liu, Z.Lou, M.Bartlam, and Z.Rao (2009).
Structure-function studies of the influenza virus RNA polymerase PA subunit.
  Sci China C Life Sci, 52, 450-458.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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