Biophysics Seminar Series

Please see below for the link to join the Zoom event.

The Biophysics Virtual Seminar Series presents:

Dr. Jamie Cate - Professor of Molecular & Cell Biology, and Chemistry,
University of California - Berkeley

“Selective modulation of human translation: potential for new therapeutics”

ABSTRACT: Small molecules that target the ribosome such as antibiotics generally impact a substantial fraction of the proteome. We recently identified a class of small molecules that bind the human ribosome and selectively stall the translation of a small subset of proteins. I will present biochemical and cell-based experiments, along with structures of human ribosome nascent chain complexes (RNCs) stalled by these compounds, determined by cryo-electron microscopy (cryo-EM). These small molecules bind in the ribosome exit tunnel in a eukaryotic-specific pocket formed by the 28S ribosomal RNA (rRNA) and arrest the translating ribosome through their interactions with the growing polypeptide chain. Intriguingly, a given compound can either inhibit or enhance translation, depending on the sequence of the protein nascent chain. These results begin to reveal how small molecules can be made to control human translation and suggest a new strategy for developing small molecules that selectively inhibit or enhance the production of proteins previously considered “undruggable.”