Related Experiment Videos
Two crystal structures demonstrate large conformational changes in the eukaryotic ribosomal translocase.
Rene Jørgensen1, Pedro A Ortiz, Anne Carr-Schmid
1Department of Molecular Biology, Aarhus University, Gustav Wieds vej 10C, DK8000 Arhus, Denmark.
Nature Structural Biology
|April 15, 2003
Summary
Crystal structures reveal yeast translation elongation factor 2 (eEF2) undergoes significant conformational changes upon binding the inhibitor sordarin. These findings provide a high-resolution basis for understanding sordarin
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Yeast translation elongation factor 2 (eEF2) is crucial for protein synthesis.
- Understanding eEF2's structure and dynamics is key to elucidating translation regulation.
- Sordarin is a known inhibitor of eEF2's function.
Purpose of the Study:
- To determine the high-resolution crystal structures of yeast eEF2.
- To investigate the structural impact of sordarin binding on eEF2 conformation.
- To provide a structural basis for sordarin's inhibitory mechanism.
Main Methods:
- X-ray crystallography was employed to determine two crystal structures.
- Structures were solved for apo yeast eEF2 at 2.9 Å resolution.
- The structure of eEF2 in complex with sordarin was determined at 2.1 Å resolution.
Main Results:
- Apo eEF2 conformation resembles its prokaryotic homolog, elongation factor G (EF-G).
- Sordarin binding induces substantial conformational changes in eEF2's C-terminal domains.
- The N-terminal nucleotide-binding domains remain largely rigid upon sordarin interaction.
- The eEF2-sordarin complex exhibits a unique conformation distinct from known EF-G structures.
Conclusions:
- The high-resolution structures elucidate the mechanism of sordarin inhibition.
- Sordarin binding triggers significant domain rearrangements in eEF2.
- These structures highlight the dynamic nature of ribosomal translocases.