Document Detail

Interaction of the Eukaryotic Initiation Factor 4E with 4E-BP2 at a Dynamic Bipartite Interface.
MedLine Citation:
PMID:  24207126     Owner:  NLM     Status:  Publisher    
Cap-dependent translation initiation is regulated by the interaction of eukaryotic initiation factor 4E (eIF4E) with eIF4E binding proteins (4E-BPs). Whereas the binding of 4E-BP peptides containing the eIF4E-binding (54)YXXXXLΦ(60) motif has been studied, atomic-level characterization of the interaction of eIF4E with full-length 4E-BPs has been lacking. Here, we use isothermal titration calorimetry and nuclear magnetic resonance spectroscopy to characterize the dynamic, structural and binding properties of 4E-BP2. Although disordered, 4E-BP2 contains significant fluctuating secondary structure and binds eIF4E at an extensive bipartite interface including the canonical (54)YXXXXLΦ(60) and (78)IPGVT(82) sites. Each of the two binding elements individually has submicromolar affinity and exchange on and off of the eIF4E surface within the context of the overall nanomolar complex. This dynamic interaction facilitates exposure of regulatory phosphorylation sites within the complex. The 4E-BP2 interface on eIF4E overlaps yet is more extensive than the eIF4G:eIF4E interface, suggesting that these key interactions may be differentially targeted for therapeutics.
Sabelo Lukhele; Alaji Bah; Hong Lin; Nahum Sonenberg; Julie D Forman-Kay
Related Documents :
2871516 - Differential effect of repeated treatment with l-dopa on dopamine-d1 or -d2 receptors.
19896846 - Synthesis and monoamine transporter affinity of 3alpha-arylmethoxy-3beta-arylnortropanes.
3522266 - Thiamine-binding activity of saccharomyces cerevisiae plasma membrane.
23108866 - The effect of cigarette smoke extract on thrombomodulin-thrombin binding: an atomic for...
3352466 - Inhibition of platelet [3h]-imipramine binding by human plasma protein fractions.
2110566 - Photoaffinity labeling and partial purification of the beta cell sulfonylurea receptor ...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-10-23
Journal Detail:
Title:  Structure (London, England : 1993)     Volume:  -     ISSN:  1878-4186     ISO Abbreviation:  Structure     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-11-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101087697     Medline TA:  Structure     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 Elsevier Ltd. All rights reserved.
Molecular Structure and Function Program, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Transient Protein States in Designing Inhibitors of the MDM2-p53 Interaction.
Next Document:  The Structural Motifs for Substrate Binding and Dimerization of the ? Subunit of Collagen Prolyl 4-H...