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Disorder guides domain rearrangement in elongation factor Tu
Author(s) -
Yang Huan,
Perrier Jonathan,
Whitford Paul C.
Publication year - 2018
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.25575
Subject(s) - conformational change , ribosome , elongation factor , elongation , translation (biology) , chemistry , biophysics , stereochemistry , crystallography , biology , biochemistry , materials science , rna , messenger rna , ultimate tensile strength , metallurgy , gene
Elongation factor Tu (EF‐Tu) is a three‐domain protein that is responsible for delivering aminoacyl‐tRNA (aa‐tRNA) molecules to the ribosome. During the delivery process, EF‐Tu undergoes a large‐scale ( ~50 Å) conformational transition that results in rearrangement of domain I, relative to the II/III superdomain. Despite the central role of EF‐Tu during protein synthesis, little is known about the structural and energetic properties of this reordering process. To study the physical‐chemical properties of domain motion, we constructed a multi‐basin structure‐based (i.e., Gō‐like) model, with which we have simulated hundreds of spontaneous conformational rearrangements. By analyzing the statistical properties of these events, we show that EF‐Tu is likely to adopt a disordered intermediate ensemble during this transition. We further show that this disordered intermediate will favor a specific sequence of conformational substeps when bound to the ribosome, and the disordered ensemble can influence the kinetics of the incoming aa‐tRNA molecule. Overall, this study highlights the dynamic nature of EF‐Tu by revealing a relationship between conformational disorder and biological function.