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PDBsum entry 3d3m

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protein Protein-protein interface(s) links
Translation PDB id
3d3m
Jmol
Contents
Protein chains
161 a.a. *
Waters ×65
* Residue conservation analysis
PDB id:
3d3m
Name: Translation
Title: The crystal structure of thE C-terminal region of death associated protein 5(dap5)
Structure: Eukaryotic translation initiation factor 4 gamma 2. Chain: a, b. Fragment: c terminal domain. Synonym: death-associated protein 5, dap-5, eif-4-gamma 2, eif-4g 2, eif4g 2, p97. Engineered: yes
Source: Homo sapiens. Man. Organism_taxid: 9606. Gene: eif4g2, dap5, ok/sw-cl.75. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.90Å     R-factor:   0.214     R-free:   0.259
Authors: O.Dym,Israel Structural Proteomics Center (Ispc)
Key ref:
N.Liberman et al. (2008). The crystal structure of the C-terminal DAP5/p97 domain sheds light on the molecular basis for its processing by caspase cleavage. J Mol Biol, 383, 539-548. PubMed id: 18722383 DOI: 10.1016/j.jmb.2008.08.013
Date:
12-May-08     Release date:   14-Oct-08    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P78344  (IF4G2_HUMAN) -  Eukaryotic translation initiation factor 4 gamma 2
Seq:
Struc:
 
Seq:
Struc:
907 a.a.
161 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1016/j.jmb.2008.08.013 J Mol Biol 383:539-548 (2008)
PubMed id: 18722383  
 
 
The crystal structure of the C-terminal DAP5/p97 domain sheds light on the molecular basis for its processing by caspase cleavage.
N.Liberman, O.Dym, T.Unger, S.Albeck, Y.Peleg, Y.Jacobovitch, A.Branzburg, M.Eisenstein, L.Marash, A.Kimchi.
 
  ABSTRACT  
 
DAP5/p97 (death-associated protein 5) is a member of the eukaryotic translation initiation factor 4G family. It functions as a scaffold protein promoting cap-independent translation of proteins. During apoptosis, DAP5/p97 is cleaved by caspases at position 792, yielding an 86-kDa C-terminal truncated isoform (DAP5/p86) that promotes translation of several mRNAs mediated by an internal ribosome entry site. In this study, we report the crystal structure of the C-terminal region of DAP5/p97 extending between amino acids 730 and 897. This structure consists of four HEAT-Repeats and is homologous to the C-terminal domain of eIF4GI, eIF5, and eIF2Bepsilon. Unlike the other proteins, DAP5/p97 lacks electron density in the loop connecting alpha3 and alpha4, which harbors the caspase cleavage site. Moreover, we observe fewer interactions between these two helices. Thus, previous mapping of this site by mutation analysis is confirmed here by the resolved structure of the DAP5/p97 C-terminus. In addition, we identified the position of two conserved aromatic and acidic boxes in the structure of the DAP5/p97 C-terminus. The acidic residues in the two aromatic and acidic boxes form a continuous negatively charged patch, which is suggested to make specific interactions with other proteins such as eIF2beta. The caspase cleavage of DAP5/p97 removes the subdomain carrying acidic residues in the AA-box motif, which may result in exposure of a hydrophobic surface. These intriguing structural differences between the two DAP5 isoforms suggest that they have different interaction partners and, subsequently, different functions.
 
  Selected figure(s)  
 
Figure 4.
Fig. 4. α3 and α4 flanking the loop containing the caspase cleavage site of DAP5-CTD in comparison to the corresponding region in eIF4GI. (a) Superposition of α3 (orange) and α4 (green) of DAP5-CTD to those of eIF4GI (blue). (b) Interacting residues between α3 and α4 of DAP5-CTD (up to 3.5 Å) and (c) between α3 and α4 of eIF4GI (up to 3.5 Å).
Figure 5.
Fig. 5. Electrostatic surface representation of DAP5-CTD. (a) Electrostatic surface representation of segment A (residues 730–788) with segment B (residues 796–897) shown in green ribbon; α4 is indicated. (b) The exposed hydrophobic surface of segment A revealed upon removal of segment B. (c) Electrostatic surface representation of DAP5-CTD showing the negative patch located in segment B [same view as in (a) and (b)].
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 383, 539-548) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20544972 S.Fan, M.Z.Jia, and W.Gong (2010).
Crystal structure of the C-terminal region of human p97/DAP5.
  Proteins, 78, 2385-2390.  
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