Biophysical Society Thematic Meeting| Lima 2019

Revisiting the Central Dogma of Molecular Biology at the Single-Molecule Level

Friday Speaker Abstracts

RIBOSOMES IN ACTION: THE ROLE OF DYNAMICS IN THE MECHANISM AND REGULATION OF TRANSLATION Ruben L Gonzalez Jr 1 ; 1 Columbia University, Department of Chemistry, New York, NY, USA Over the past two decades, stunning breakthroughs in the field of structural biology have continued to produce groundbreaking high-resolution structures of the ribosome and the rest of the cellular translation machinery (TM) that translates messenger RNAs (mRNAs) into proteins, an essential step in the central dogma of molecular biology. Comparative analyses of these static structures reveal the remarkable conformational flexibility of the TM and hint at the significant structural rearrangements that evidently accompany its functional cycle. Unfortunately, the experimental observation and characterization of these conformational dynamics is significantly impeded by the size and complexity of the TM, severely limiting our understanding of the contributions that dynamics make to its function. In my talk, I will present recent and ongoing work form my research group in which we have combined single-molecule fluorescence imaging with complementary structural and biochemical approaches to overcome these challenges and elucidate the precise roles that the conformational dynamics of the TM play in driving and controlling protein synthesis. In particular, I will focus on how thermally driven fluctuations of the ribosome and other essential components of the TM contribute to the mechanism and regulation of translation. Because the ribosome is the target of over half of all currently prescribed antibiotics and because of the growing list of human diseases to which dysregulation of translation has been causally linked, our findings hold great promise for informing the development of next-generation antibiotics and small-molecule therapeutic agents that function by modulating the conformational dynamics of the TM. To this end, I will close my talk by discussing what we envision lies ahead as single-molecule fluorescence imaging continues to evolve and expand such that it can address increasingly complex mechanistic and regulatory aspects of this fundamental biological process.

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