MD and Docking Studies Reveal That the Functional Switch of CYFIP1 is Mediated by a Butterfly-like Motion.

Détails

ID Serval
serval:BIB_F136232E6474
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
MD and Docking Studies Reveal That the Functional Switch of CYFIP1 is Mediated by a Butterfly-like Motion.
Périodique
Journal of chemical theory and computation
Auteur(s)
Di Marino D., Chillemi G., De Rubeis S., Tramontano A., Achsel T., Bagni C.
ISSN
1549-9626 (Electronic)
ISSN-L
1549-9618
Statut éditorial
Publié
Date de publication
14/07/2015
Volume
11
Numéro
7
Pages
3401-3410
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Cytoplasmic FMRP interacting protein 1 (CYFIP1), also known as specifically RAC1 activated protein 1 (Sra1), plays a dual role: together with fragile X mental retardation protein (FMRP) and eIF4E it forms a complex that inhibits mRNA translation, while together with WAVE1, NCKAP1, ABI2, and HSPC300 it forms the WAVE regulatory complex (WRC) that upon RAC1 activation initiates actin polymerization. Here we performed a molecular dynamics (MD) simulation on CYFIP1 extracted from the known WRC structure, which shows that, in the absence of its WRC partners, a butterfly-like motion brings the two ends of CYFIP1 closer together, enabling the interaction with eIF4E. Our MD simulation is supported by available data showing that binding of CYFIP1 to eIF4E and binding to the WRC are mutually exclusive and that there is fluorescence resonance energy transfer between the N- and C-termini of CYFIP1. The differential interaction of RAC1-GTP with the two CYFIP1 structures predicts that RAC1 is directly responsible for the switch between these conformations.

Mots-clé
Adaptor Proteins, Signal Transducing/chemistry, Humans, Molecular Docking Simulation, Molecular Dynamics Simulation, Movement
Pubmed
Création de la notice
06/03/2017 18:23
Dernière modification de la notice
03/03/2018 22:38
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