Dr
Michal H. Kolář
(University of Chemistry and Technology, Prague, Czech Republic)
VemP is a peptide found in a marine bacterium, which can live in fresh or salt water. VemP regulates how other proteins are transported out of the bacterium under different extracellular ionic concentrations. The regulation mechanism involves ribosome stalling, which modulates the protein synthesis. Many physiologic consequences have been identified to be stalling-dependent; apart from the protein excretion also the effect of antibiotics, or protein misfolding.
In case of VemP, the stalling is caused by a unique α-helical element formed in the exit tunnel near the catalytic center. The helix interferes with several ribosome residues, which are critical for peptide bond formation. We have probed the structure and dynamics of VemP in the stalled ribosome as well as in the aqueous solution. We have proposed, why the stalling efficiency depends on many more nascent peptide amino acids than in other regulatory nascent peptides. While the amino acids of the VemP helix directly inhibit the peptide synthesis, the more distant VemP parts hold the α-helix in place so it is effective. Also, the simulations suggest that the tunnel walls play a critical role in VemP folding.
Our simulations include entire ribosome dissolved in explicit aqueous environment under physiological conditions totaling in more than 2 million particles in the simulation box. Such a challenging setup requires large-scale supercomputer facilities to sample conformational space at relevant time scales. Apart from IT4I resources, we have employed two German supercomputers, namely SUPERMUC in Munich and Hazel Hen in Stuttgart via their respective Open calls.
Summary
Proteins are key biomolecules consisting of chains of amino acids. In all living organisms, the chemical bonds between the amino acids are formed in cellular nanomachines called ribosomes [1]. Because the chemical reactions happen deep inside the ribosome, the newly synthesized protein - also called nascent protein - leaves the ribosome through a tunnel. Only little is known about what happens inside the ribosome tunnel before the nascent protein exits it. By means of all-atom molecular dynamics simulations, we have studied how the ribosome is regulated by a nascent peptide called VemP.
References
[1] LV Bock, MH Kolář, H Grubmüller: Molecular simulations of the ribosome and associated translation factors. Current Opinion in Structural Biology 2018, 27-35.
Dr
Michal H. Kolář
(University of Chemistry and Technology, Prague, Czech Republic)
Prof.
Helmut Grubmüller
(Max Planck Institute for Biophysical Chemistry, Göttingen, Germany)
Dr
Lars V. Bock
(Max Planck Institute for Biophysical Chemistry, Göttingen, Germany)
