Two Crystal Structures Demonstrate Large Conformational Changes in the Eukaryotic Ribosomal Translocase

Document Type

Article

Publication Title

Nature Structural & Molecular Biology

Publication Date

4-14-2003

Abstract

Two crystal structures of yeast translation elongation factor 2 (eEF2) were determined: the apo form at 2.9 Å resolution and eEF2 in the presence of the translocation inhibitor sordarin at 2.1 Å resolution. The overall conformation of apo eEF2 is similar to that of its prokaryotic homolog elongation factor G (EF-G) in complex with GDP. Upon sordarin binding, the three tRNA-mimicking C-terminal domains undergo substantial conformational changes, while the three N-terminal domains containing the nucleotide-binding site form an almost rigid unit. The conformation of eEF2 in complex with sordarin is entirely different from known conformations observed in crystal structures of EF-G or from cryo-EM studies of EF-G–70S complexes. The domain rearrangements induced by sordarin binding and the highly ordered drug-binding site observed in the eEF2–sordarin structure provide a high-resolution structural basis for the mechanism of sordarin inhibition. The two structures also emphasize the dynamic nature of the ribosomal translocase.

DOI

10.1038/nsb923

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