2xb2

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Crystal structure of the core Mago-Y14-eIF4AIII-Barentsz-UPF3b assembly shows how the EJC is bridged to the NMD machinery

Structural highlights

2xb2 is a 13 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.4Å
Ligands:ANP, MG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

REN3B_HUMAN FG syndrome;X-linked intellectual disability with marfanoid habitus;X-linked non-syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry.[1]

Function

REN3B_HUMAN Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF2 stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA upstream of exon-exon junctions. In vitro, stimulates translation; the function is independent of association with UPF2 and components of the EJC core.[2] [3] [4] [5] [6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

In mammals, Up-frameshift proteins (UPFs) form a surveillance complex that interacts with the exon junction complex (EJC) to elicit nonsense-mediated mRNA decay (NMD). UPF3b is the component of the surveillance complex that bridges the interaction with the EJC. Here, we report the 3.4 A resolution crystal structure of a minimal UPF3b-EJC assembly, consisting of the interacting domains of five proteins (UPF3b, MAGO, Y14, eIF4AIII, and Barentsz) together with RNA and adenylyl-imidodiphosphate. Human UPF3b binds with the C-terminal domain stretched over a composite surface formed by eIF4AIII, MAGO, and Y14. Residues that affect NMD when mutated are found at the core interacting surfaces, whereas differences between UPF3b and UPF3a map at peripheral interacting residues. Comparison with the binding mode of the protein PYM underscores how a common molecular surface of MAGO and Y14 recognizes different proteins acting at different times in the same pathway. The binding mode to eIF4AIII identifies a surface hot spot that is used by different DEAD-box proteins to recruit their regulators.

Insights into the recruitment of the NMD machinery from the crystal structure of a core EJC-UPF3b complex.,Buchwald G, Ebert J, Basquin C, Sauliere J, Jayachandran U, Bono F, Le Hir H, Conti E Proc Natl Acad Sci U S A. 2010 May 17. PMID:20479275[7]

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

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Citations
32 reviews cite this structure
From unwinding to clamping - the DEAD box RNA helicase family.
Linder et al. (2011)
31 more
42 other articles
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See Also

References

  1. ↑ Tarpey PS, Raymond FL, Nguyen LS, Rodriguez J, Hackett A, Vandeleur L, Smith R, Shoubridge C, Edkins S, Stevens C, O'Meara S, Tofts C, Barthorpe S, Buck G, Cole J, Halliday K, Hills K, Jones D, Mironenko T, Perry J, Varian J, West S, Widaa S, Teague J, Dicks E, Butler A, Menzies A, Richardson D, Jenkinson A, Shepherd R, Raine K, Moon J, Luo Y, Parnau J, Bhat SS, Gardner A, Corbett M, Brooks D, Thomas P, Parkinson-Lawrence E, Porteous ME, Warner JP, Sanderson T, Pearson P, Simensen RJ, Skinner C, Hoganson G, Superneau D, Wooster R, Bobrow M, Turner G, Stevenson RE, Schwartz CE, Futreal PA, Srivastava AK, Stratton MR, Gecz J. Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation. Nat Genet. 2007 Sep;39(9):1127-33. Epub 2007 Aug 19. PMID:17704778 doi:http://dx.doi.org/10.1038/ng2100
  2. ↑ Lykke-Andersen J, Shu MD, Steitz JA. Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon. Cell. 2000 Dec 22;103(7):1121-31. PMID:11163187
  3. ↑ Gehring NH, Neu-Yilik G, Schell T, Hentze MW, Kulozik AE. Y14 and hUpf3b form an NMD-activating complex. Mol Cell. 2003 Apr;11(4):939-49. PMID:12718880
  4. ↑ Gehring NH, Kunz JB, Neu-Yilik G, Breit S, Viegas MH, Hentze MW, Kulozik AE. Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements. Mol Cell. 2005 Oct 7;20(1):65-75. PMID:16209946 doi:http://dx.doi.org/S1097-2765(05)01554-6
  5. ↑ Kunz JB, Neu-Yilik G, Hentze MW, Kulozik AE, Gehring NH. Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation. RNA. 2006 Jun;12(6):1015-22. Epub 2006 Apr 6. PMID:16601204 doi:http://dx.doi.org/10.1261/rna.12506
  6. ↑ Chamieh H, Ballut L, Bonneau F, Le Hir H. NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity. Nat Struct Mol Biol. 2008 Jan;15(1):85-93. Epub 2007 Dec 9. PMID:18066079 doi:http://dx.doi.org/10.1038/nsmb1330
  7. ↑ Buchwald G, Ebert J, Basquin C, Sauliere J, Jayachandran U, Bono F, Le Hir H, Conti E. Insights into the recruitment of the NMD machinery from the crystal structure of a core EJC-UPF3b complex. Proc Natl Acad Sci U S A. 2010 May 17. PMID:20479275

Contents


PDB ID 2xb2

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