PDBsum entry 2p8r

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protein links
Splicing PDB id
Protein chain
246 a.a. *
Waters ×167
* Residue conservation analysis
PDB id:
Name: Splicing
Title: Crystal structure of thE C-terminal domain of c. Elegans pre splicing factor prp8 carrying r2303k mutant
Structure: Pre-mRNA-splicing factor prp8. Chain: a. Fragment: c-terminal domain. Synonym: prp8. Engineered: yes. Mutation: yes
Source: Caenorhabditis elegans. Organism_taxid: 6239. Gene: prp-8. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.10Å     R-factor:   0.230     R-free:   0.248
Authors: L.Zhang,J.Shen,M.T.Guarnieri,A.Heroux,K.Yang,R.Zhao
Key ref:
L.Zhang et al. (2007). Crystal structure of the C-terminal domain of splicing factor Prp8 carrying retinitis pigmentosa mutants. Protein Sci, 16, 1024-1031. PubMed id: 17473007 DOI: 10.1110/ps.072872007
22-Mar-07     Release date:   22-May-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P34369  (PRP8_CAEEL) -  Pre-mRNA-splicing factor 8 homolog
2329 a.a.
246 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     spliceosomal complex   1 term 
  Biological process     nuclear mRNA splicing, via spliceosome   1 term 


DOI no: 10.1110/ps.072872007 Protein Sci 16:1024-1031 (2007)
PubMed id: 17473007  
Crystal structure of the C-terminal domain of splicing factor Prp8 carrying retinitis pigmentosa mutants.
L.Zhang, J.Shen, M.T.Guarnieri, A.Heroux, K.Yang, R.Zhao.
Prp8 is a critical pre-mRNA splicing factor. Prp8 is proposed to help form and stabilize the spliceosome catalytic core and to be an important regulator of spliceosome activation. Mutations in human Prp8 (hPrp8) cause a severe form of the genetic disorder retinitis pigmentosa, RP13. Understanding the molecular mechanism of Prp8's function in pre-mRNA splicing and RP13 has been hindered by its large size (over 2000 amino acids) and remarkably low-sequence similarity with other proteins. Here we present the crystal structure of the C-terminal domain (the last 273 residues) of Caenorhabditis elegans Prp8 (cPrp8). The core of the C-terminal domain is an alpha/beta structure that forms the MPN (Mpr1, Pad1 N-terminal) fold but without Zn(2+) coordination. We propose that the C-terminal domain is a protein interaction domain instead of a Zn(2+)-dependent metalloenzyme as proposed for some MPN proteins. Mapping of RP13 mutants on the Prp8 structure suggests that these residues constitute a binding surface between Prp8 and other partner(s), and the disruption of this interaction provides a plausible molecular mechanism for RP13.
  Selected figure(s)  
Figure 4.
Figure 4. RP13 mutations. (A, left) Residues corresponding to the human RP13 mutations (ball and stick models) are located on the
  The above figure is reprinted by permission from the Protein Society: Protein Sci (2007, 16, 1024-1031) copyright 2007.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23354046 W.P.Galej, C.Oubridge, A.J.Newman, and K.Nagai (2013).
Crystal structure of Prp8 reveals active site cavity of the spliceosome.
  Nature, 493, 638-643.
PDB codes: 3zef 4i43
21080498 S.Valadkhan, and Y.Jaladat (2010).
The spliceosomal proteome: at the heart of the largest cellular ribonucleoprotein machine.
  Proteomics, 10, 4128-4141.  
19098916 C.Maeder, A.K.Kutach, and C.Guthrie (2009).
ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires the C terminus of Prp8.
  Nat Struct Mol Biol, 16, 42-48.  
19447915 C.Netter, G.Weber, H.Benecke, and M.C.Wahl (2009).
Functional stabilization of an RNA recognition motif by a noncanonical N-terminal expansion.
  RNA, 15, 1305-1313.
PDB code: 3egn
19125166 D.A.Brow (2009).
Eye on RNA unwinding.
  Nat Struct Mol Biol, 16, 7-8.  
19243136 F.E.Reyes-Turcu, and K.D.Wilkinson (2009).
Polyubiquitin binding and disassembly by deubiquitinating enzymes.
  Chem Rev, 109, 1495-1508.  
19525970 L.Zhang, T.Xu, C.Maeder, L.O.Bud, J.Shanks, J.Nix, C.Guthrie, J.A.Pleiss, and R.Zhao (2009).
Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2.
  Nat Struct Mol Biol, 16, 731-739.
PDB code: 3hib
19239890 M.C.Wahl, C.L.Will, and R.Lührmann (2009).
The spliceosome: design principles of a dynamic RNP machine.
  Cell, 136, 701-718.  
18461042 C.Maeder, and C.Guthrie (2008).
Modifications target spliceosome dynamics.
  Nat Struct Mol Biol, 15, 426-428.  
19050716 J.Abelson (2008).
Is the spliceosome a ribonucleoprotein enzyme?
  Nat Struct Mol Biol, 15, 1235-1237.  
19000813 J.Sperling, M.Azubel, and R.Sperling (2008).
Structure and function of the Pre-mRNA splicing machine.
  Structure, 16, 1605-1615.  
18779563 K.Yang, L.Zhang, T.Xu, A.Heroux, and R.Zhao (2008).
Crystal structure of the beta-finger domain of Prp8 reveals analogy to ribosomal proteins.
  Proc Natl Acad Sci U S A, 105, 13817-13822.
PDB code: 3e66
  19096719 L.Ivings, K.V.Towns, M.A.Matin, C.Taylor, F.Ponchel, R.J.Grainger, R.S.Ramesar, D.A.Mackey, and C.F.Inglehearn (2008).
Evaluation of splicing efficiency in lymphoblastoid cell lines from patients with splicing-factor retinitis pigmentosa.
  Mol Vis, 14, 2357-2366.  
18945809 M.Hebeisen, J.Drysdale, and R.Roy (2008).
Suppressors of the cdc-25.1(gf)-associated intestinal hyperplasia reveal important maternal roles for prp-8 and a subset of splicing factors in C. elegans.
  RNA, 14, 2618-2633.  
18550358 M.S.Jurica (2008).
Detailed close-ups and the big picture of spliceosomes.
  Curr Opin Struct Biol, 18, 315-320.  
18425143 P.Bellare, E.C.Small, X.Huang, J.A.Wohlschlegel, J.P.Staley, and E.J.Sontheimer (2008).
A role for ubiquitin in the spliceosome assembly pathway.
  Nat Struct Mol Biol, 15, 444-451.  
18843295 V.Pena, A.Rozov, P.Fabrizio, R.Lührmann, and M.C.Wahl (2008).
Structure and function of an RNase H domain at the heart of the spliceosome.
  EMBO J, 27, 2929-2940.
PDB codes: 3e9l 3e9o 3e9p
18758443 Y.Sato, A.Yoshikawa, A.Yamagata, H.Mimura, M.Yamashita, K.Ookata, O.Nureki, K.Iwai, M.Komada, and S.Fukai (2008).
Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains.
  Nature, 455, 358-362.
PDB codes: 2znr 2znv
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.