Two crystal structures demonstrate large conformational changes in the eukaryotic ribosomal translocase.
Two crystal structures of yeast translation elongation factor 2 (eEF2) were determined: the apo form at 2.9 A resolution and eEF2 in the presence of the translocation inhibitor sordarin at 2.1 A 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.
Jørgensen
Rene
R
Department of Molecular Biology, Aarhus University, Gustav Wieds vej 10C, DK8000 Arhus, Denmark.
Ortiz
Pedro A
PA
Carr-Schmid
Anne
A
Nissen
Poul
P
Kinzy
Terri Goss
TG
Andersen
Gregers Rom
GR
D000595:Amino Acid Sequence; D001059:Apoproteins / Q000737:chemistry / Q000648:ultrastructure; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008969:Molecular Sequence Data; D020652:Peptide Elongation Factor 2 / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D011487:Protein Conformation; D012270:Ribosomes / Q000235:genetics / Q000648:ultrastructure*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000648:ultrastructure*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure
D001059:Apoproteins; D020652:Peptide Elongation Factor 2; D029701:Saccharomyces cerevisiae Proteins