Literature DB >> 27162083

The Role of Dynamics and Allostery in the Inhibition of the eIF4E/eIF4G Translation Initiation Factor Complex.

Nicola Salvi1,2, Evangelos Papadopoulos3, Martin Blackledge4, Gerhard Wagner5.   

Abstract

Lack of regulation of the interaction between the eIF4E/eIF4G subunits of the translation initiation factor complex eIF4F is a hallmark of cancer. The inhibitor 4EGI-1 binds to eIF4E, thereby preventing association with eIF4G through an allosteric mechanism. NMR spectroscopy and MD simulations were used to obtain a mechanistic description of the role of correlated dynamics in this allosteric regulation. We show that binding of 4EGI-1 perturbs native correlated motions and increases correlated fluctuations in part of the eIF4G binding site.
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Entities:  

Keywords:  NMR spectroscopy; allosterism; inhibitors; molecular dynamics; protein-protein interactions

Mesh：

Substances：

Year:  2016        PMID： 27162083      PMCID： PMC5022372          DOI： 10.1002/anie.201603254

Source DB:  PubMed          Journal:  Angew Chem Int Ed Engl        ISSN： 1433-7851            Impact factor:   15.336


  22 in total

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4.  Molecular architecture of 4E-BP translational inhibitors bound to eIF4E.

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Journal:  Mol Cell       Date:  2015-02-19       Impact factor: 17.970

5.  Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G.

Authors:  Evangelos Papadopoulos; Simon Jenni; Eihab Kabha; Khuloud J Takrouri; Tingfang Yi; Nicola Salvi; Rafael E Luna; Evripidis Gavathiotis; Poornachandran Mahalingam; Haribabu Arthanari; Ricard Rodriguez-Mias; Revital Yefidoff-Freedman; Bertal H Aktas; Michael Chorev; Jose A Halperin; Gerhard Wagner
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6.  Structural insights into the allosteric effects of 4EBP1 on the eukaryotic translation initiation factor eIF4E.

Authors:  Nadeem Siddiqui; Wolfram Tempel; Lucy Nedyalkova; Laurent Volpon; Amy K Wernimont; Michael J Osborne; Hee-Won Park; Katherine L B Borden
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Authors:  Jeremy R Graff; Bruce W Konicek; Rebecca L Lynch; Chad A Dumstorf; Michele S Dowless; Ann M McNulty; Stephen H Parsons; Leslie H Brail; Bruce M Colligan; Jonathan W Koop; Bernadette M Hurst; James A Deddens; Blake L Neubauer; Louis F Stancato; Harry W Carter; Larry E Douglass; Julia H Carter
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Authors:  Gemma Armengol; Federico Rojo; Josep Castellví; Carmela Iglesias; Miriam Cuatrecasas; Berta Pons; José Baselga; Santiago Ramón y Cajal
Journal:  Cancer Res       Date:  2007-08-15       Impact factor: 12.701

10.  4EGI-1 targets breast cancer stem cells by selective inhibition of translation that persists in CSC maintenance, proliferation and metastasis.

Authors:  Tingfang Yi; Eihab Kabha; Evangelos Papadopoulos; Gerhard Wagner
Journal:  Oncotarget       Date:  2014-08-15
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  6 in total

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2.  Structural studies of the eIF4E-VPg complex reveal a direct competition for capped RNA: Implications for translation.

Authors:  Luciana Coutinho de Oliveira; Laurent Volpon; Amanda K Rahardjo; Michael J Osborne; Biljana Culjkovic-Kraljacic; Christian Trahan; Marlene Oeffinger; Benjamin H Kwok; Katherine L B Borden
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5.  Non-cooperative 4E-BP2 folding with exchange between eIF4E-binding and binding-incompatible states tunes cap-dependent translation inhibition.

Authors:  Jennifer E Dawson; Alaji Bah; Zhenfu Zhang; Robert M Vernon; Hong Lin; P Andrew Chong; Manasvi Vanama; Nahum Sonenberg; Claudiu C Gradinaru; Julie D Forman-Kay
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6.  A newly identified Leishmania IF4E-interacting protein, Leish4E-IP2, modulates the activity of cap-binding protein paralogs.

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