Monday, August 8, 2011

Structure of a no-go mRNA decay complex bound to a stalled 80S ribosome

A recent work by the Beckmann group (University of Munich, Germany) published in Nature Structural and Molecular Biology describes a sub-nanometer cryo-EM reconstruction of a no-go mRNA decay complex bound to a stalled 80S ribosome. Homology models were manually docked into the density and further refined interactively with MDFF.

Structure of the no-go mRNA decay complex Dom34-Hbs1 bound to a stalled 80S ribosome.
Thomas Becker, Jean-Paul Armache, Alexander Jarasch, Andreas M Anger, Elizabeth Villa, Heidemarie Sieber, Basma Abdel Motaal, Thorsten Mielke, Otto Berninghausen, and Roland Beckmann. Nat. Struct. Mol. Biol., 18, 715-720, 2011.

No-go decay (NGD) is a mRNA quality-control mechanism in eukaryotic cells that leads to degradation of mRNAs stalled during translational elongation. The key factors triggering NGD are Dom34 and Hbs1. We used cryo-EM to visualize NGD intermediates resulting from binding of the Dom34–Hbs1 complex to stalled ribosomes. At subnanometer resolution, all domains of Dom34 and Hbs1 were identified, allowing the docking of crystal structures and homology models. Moreover, the close structural similarity of Dom34 and Hbs1 to eukaryotic release factors (eRFs) enabled us to propose a model for the ribosome-bound eRF1–eRF3 complex. Collectively, our data provide structural insights into how stalled mRNA is recognized on the ribosome and how the eRF complex can simultaneously recognize stop codons and catalyze peptide release.

Monday, August 1, 2011

Correcting and preventing stereochemical errors

A recent publication at BMC Bioinformatics describes two VMD plugins that can be used to detect, visualize, and correct stereochemical errors in macromolecular structures. The plugins can also be used to generate restraints that prevent chirality and peptide bond configuration errors from arising in simulations where high forces are applied, such as MDFF simulations. Use of the plugins is described in the Structure Check Tutorial.

Stereochemical errors and their implications for molecular dynamics simulations.
Eduard Schreiner, Leonardo G. Trabuco, Peter L. Freddolino, and Klaus Schulten. BMC Bioinformatics, 12, 190, 2011.

Background: Biological molecules are often asymmetric with respect to stereochemistry, and correct stereochemistry is essential to their function. Molecular dynamics simulations of biomolecules have increasingly become an integral part of biophysical research. However, stereochemical errors in biomolecular structures can have a dramatic impact on the results of simulations.

Results: Here we illustrate the effects that chirality and peptide bond configuration flips may have on the secondary structure of proteins throughout a simulation. We also analyze the most common sources of stereochemical errors in biomolecular structures and present software tools to identify, correct, and prevent stereochemical errors in molecular dynamics simulations of biomolecules.

Conclusions: Use of the tools presented here should become a standard step in the preparation of biomolecular simulations.