Structural analysis of the DAP5 MIF4G domain and its interaction with eIF4A

Geneviève Virgili, Filipp Frank, Kateryna Feoktistova, Maxime Sawicki, Nahum Sonenberg, Christopher S. Fraser, Bhushan Nagar

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Death-associated protein 5 (DAP5/p97) is a homolog of the eukaryotic initiation factor 4G (eIF4G) that promotes the IRES-driven translation of multiple cellular mRNAs. Central to its function is the middle domain (MIF4G), which recruits the RNA helicase eIF4A. The middle domain of eIF4G consists of tandem HEAT repeats that coalesce to form a solenoid-type structure. Here, we report the crystal structure of the DAP5 MIF4G domain. Its overall fold is very similar to that of eIF4G; however, significant conformational variations impart distinct surface properties that could explain the observed differences in IRES binding between the two proteins. Interestingly, quantitative analysis of the DAP5-eIF4A interaction using isothermal titration calorimetry reveals a 10-fold lower affinity than with the eIF4G-eIF4A interaction that appears to affect their ability to stimulate eIF4A RNA unwinding activity in vitro. This difference in stability of the complex may have functional implications in selecting the mode of translation initiation.

Original languageEnglish (US)
Pages (from-to)517-527
Number of pages11
JournalStructure
Volume21
Issue number4
DOIs
StatePublished - Apr 2 2013

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Eukaryotic Initiation Factor-4G
RNA Helicases
Calorimetry
Tandem Repeat Sequences
Surface Properties
Proteins
RNA
Messenger RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Virgili, G., Frank, F., Feoktistova, K., Sawicki, M., Sonenberg, N., Fraser, C. S., & Nagar, B. (2013). Structural analysis of the DAP5 MIF4G domain and its interaction with eIF4A. Structure, 21(4), 517-527. https://doi.org/10.1016/j.str.2013.01.015

Structural analysis of the DAP5 MIF4G domain and its interaction with eIF4A. / Virgili, Geneviève; Frank, Filipp; Feoktistova, Kateryna; Sawicki, Maxime; Sonenberg, Nahum; Fraser, Christopher S.; Nagar, Bhushan.

In: Structure, Vol. 21, No. 4, 02.04.2013, p. 517-527.

Research output: Contribution to journalArticle

Virgili, G, Frank, F, Feoktistova, K, Sawicki, M, Sonenberg, N, Fraser, CS & Nagar, B 2013, 'Structural analysis of the DAP5 MIF4G domain and its interaction with eIF4A', Structure, vol. 21, no. 4, pp. 517-527. https://doi.org/10.1016/j.str.2013.01.015
Virgili G, Frank F, Feoktistova K, Sawicki M, Sonenberg N, Fraser CS et al. Structural analysis of the DAP5 MIF4G domain and its interaction with eIF4A. Structure. 2013 Apr 2;21(4):517-527. https://doi.org/10.1016/j.str.2013.01.015
Virgili, Geneviève ; Frank, Filipp ; Feoktistova, Kateryna ; Sawicki, Maxime ; Sonenberg, Nahum ; Fraser, Christopher S. ; Nagar, Bhushan. / Structural analysis of the DAP5 MIF4G domain and its interaction with eIF4A. In: Structure. 2013 ; Vol. 21, No. 4. pp. 517-527.
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