Structural highlights
Function
[IF4G2_HUMAN] Appears to play a role in the switch from cap-dependent to IRES-mediated translation during mitosis, apoptosis and viral infection. Cleaved by some caspases and viral proteases.[1] [2] [3] [4]
Publication Abstract from PubMed
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.
Structural Analysis of the DAP5 MIF4G Domain and Its Interaction with eIF4A.,Virgili G, Frank F, Feoktistova K, Sawicki M, Sonenberg N, Fraser CS, Nagar B Structure. 2013 Mar 5. pii: S0969-2126(13)00023-3. doi:, 10.1016/j.str.2013.01.015. PMID:23478064[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Imataka H, Olsen HS, Sonenberg N. A new translational regulator with homology to eukaryotic translation initiation factor 4G. EMBO J. 1997 Feb 17;16(4):817-25. PMID:9049310 doi:10.1093/emboj/16.4.817
- ↑ Levy-Strumpf N, Deiss LP, Berissi H, Kimchi A. DAP-5, a novel homolog of eukaryotic translation initiation factor 4G isolated as a putative modulator of gamma interferon-induced programmed cell death. Mol Cell Biol. 1997 Mar;17(3):1615-25. PMID:9032289
- ↑ Pyronnet S, Dostie J, Sonenberg N. Suppression of cap-dependent translation in mitosis. Genes Dev. 2001 Aug 15;15(16):2083-93. PMID:11511540 doi:10.1101/gad.889201
- ↑ Henis-Korenblit S, Shani G, Sines T, Marash L, Shohat G, Kimchi A. The caspase-cleaved DAP5 protein supports internal ribosome entry site-mediated translation of death proteins. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5400-5. Epub 2002 Apr 9. PMID:11943866 doi:10.1073/pnas.082102499
- ↑ Virgili G, Frank F, Feoktistova K, Sawicki M, Sonenberg N, Fraser CS, Nagar B. Structural Analysis of the DAP5 MIF4G Domain and Its Interaction with eIF4A. Structure. 2013 Mar 5. pii: S0969-2126(13)00023-3. doi:, 10.1016/j.str.2013.01.015. PMID:23478064 doi:http://dx.doi.org/10.1016/j.str.2013.01.015
