4IUL

MIF4G domain of DAP5

Summary for 4IUL

• Entry DOI: 10.2210/pdb4iul/pdb
• Descriptor: Eukaryotic translation initiation factor 4 gamma 2, SULFATE ION (3 entities in total)
• Functional Keywords: heat repeats, protein-protein interaction, eif4a, translation
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 61962.03

Authors

Frank, F.,Virgili, G.,Feoktistova, K.,Sawicki, M.,Sonenberg, N.,Fraser, C.,Nagar, B. (deposition date: 2013-01-21, release date: 2013-03-27, Last modification date: 2023-09-20)

Primary citation

Virgili, G.,Frank, F.,Feoktistova, K.,Sawicki, M.,Sonenberg, N.,Fraser, C.S.,Nagar, B.
Structural Analysis of the DAP5 MIF4G Domain and Its Interaction with eIF4A.
Structure, 21:517-527, 2013

PubMed 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.

PubMed: 23478064
DOI: 10.1016/j.str.2013.01.015

Experimental method

X-RAY DIFFRACTION (2.3 Å)