\nMost proteins begin to fold co-translationally on the ribosome while they
\nemerge from its exit tunnel during protein biosynthesis. This is a
\nfundamental process for maintaining cellular proteostasis, failure of which
\nresults in polypeptide misfolding and diseases such as Parkinson\u2019s,
\nAlzheimer\u2019s or other proteinopathies. Despite its importance, it remains
\npoorly understood as it is a significant challenge to obtain
\nhigh-resolution structural data of co-translational protein folding (coTF)
\nusing structural biology methods alone; particularly the description of the
\nfolding pathways is missing. Consequently, the use of accurate and
\nefficient computational techniques, especially in combination with NMR and
\ncryo-EM experimental data used as restraints, for reweighting or
\nvalidation, is imperative for a detailed understanding of protein folding
\nin the cell. In this presentation, I will describe an integrative
\nstructural biology approach to study co-translational protein folding,
\ncombining bioinformatics, all-atom and coarse-grained molecular dynamics
\n(MD) simulations with structural restraints from various experimental data
\n(NMR chemical shifts, RDCs and cryo-EM maps) and applied it to provide a
\nhigh-resolution description of snapshots of the protein biosynthesis. I
\nwill present the characterisation of the dynamics and interactions of both
\nfolded and intrinsically disordered nascent chains on the wild-type
\nbacterial ribosome and the rationally designed ribosome based on
\nbioinformatics analysis. Finally, I will provide the first structural
\ninsights into the co-translational folding intermediate that were
\nexperimentally confirmed and are the first step to fully characterising the
\nco-translational folding pathway.<\/p>\n","protected":false},"excerpt":{"rendered":"
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<\/a>SEMINARIUM Z FIZYKI BIOLOGICZNEJ I BIOINFORMATYKI Instytutu Biochemii i Biofizyki PAN, Instytutu Fizyki PAN, i Zak\u0142adu Biofizyki UW Wednesday, 19.04.2023, 15:15 https:\/\/zoom.us\/j\/91976153012?pwd=azNiMWE4UnhPN3lRQlY2UHZHOXVkQT09 „A computational microscope to study co-translational protein folding” Dr Tomasz W\u0142odarski Department of Structural and Molecular Biology University … Czytaj dalej