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Molecular Mechanism of the Ded1p-eIF4F Complex

Gao, Zhaofeng
http://rave.ohiolink.edu/etdc/view?acc_num=case1467824941

Abstract Details

2016, Doctor of Philosophy, Case Western Reserve University, Biochemistry.
The eukaryotic translation initiation factor 4F (eIF4F) consists of the large scaffolding and RNA binding protein eIF4G, the cap-binding protein eIF4E, and the DEAD-box RNA helicase eIF4A. In Saccharomyces cerevisiae, another DEAD-box RNA helicase, Ded1p, is also required for translation initiation. Here we show that eIF4A and Ded1p directly interact with each other and simultaneously with eIF4G. Both eIF4A and eIF4G interfere with the oligomerization of Ded1p. We delineate a comprehensive thermodynamic framework for the interactions between Ded1p, eIF4A, eIF4G, RNA and ATP, which indicates that eIF4A, with and without eIF4G, acts as modulator for activity and substrate preferences of Ded1p, which is the RNA remodeling unit in all complexes. We further show that Ded1p allows eIF4F to associate with short RNAs, which eIF4F alone cannot bind. Ded1p also dramatically enhances the binding of eIF4F to the 5’-cap. Our results reveal and characterize an unexpected interdependence between the two RNA helicases and eIF4G, and suggest that Ded1p is an integral part of eIF4F.
Eckhard Jankowsky (Advisor)
William Merrick (Committee Chair)
Coller Jeff (Committee Member)
Derek Taylor (Committee Member)
Blanton Tolbert (Committee Member)
216 p.
Biochemistry
DEAD-box RNA helicases, translation initiation, Ded1p, eIF4A, eIF4G, eIF4E, eIF4F

Recommended Citations

Citations

  • Gao, Z. (2016). Molecular Mechanism of the Ded1p-eIF4F Complex [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1467824941

    APA Style (7th edition)

  • Gao, Zhaofeng. Molecular Mechanism of the Ded1p-eIF4F Complex . 2016. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1467824941.

    MLA Style (8th edition)

  • Gao, Zhaofeng. "Molecular Mechanism of the Ded1p-eIF4F Complex ." Doctoral dissertation, Case Western Reserve University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1467824941

    Chicago Manual of Style (17th edition)

case1467824941
333
© 2016, some rights reserved.Creative Commons License Molecular Mechanism of the Ded1p-eIF4F Complex by Zhaofeng Gao is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.