Protein synthesis (translation) requires the ribosome to undergo multifaceted motions, including intersubunit rotation and intrasubunit head swivel. For example, intersubunit rotation involves the movement of the small subunit relative to the large subunit, while intrasubunit head swivel refers to the motion of the small subunit’s head domain relative to its body domain. Key biochemical and structural data indicate that there are several more intricate motions of the ribosome that are essential to translation but remain poorly explored, particularly in the process of small and large subunit joining during translation initiation. Our group utilizes pre-steady state kinetics, single-molecule approaches, cryo-electron microscopy, and molecular dynamics simulations to investigate the ribosomal movements that enable translation to proceed.
In the Girodat lab, we investigate the movements of the ribosome as a potential target for antibiotic development. Several antibiotics have been shown to inhibit essential ribosomal movements, stalling the process of translation. By providing a thorough understanding of how ribosomes move, we aim to gain insights into which motions can be inhibited for the development of the next generation of antibiotics.