Biophysics Seminar- “Understanding microtubule nucleation through the conformational dynamics of α, β, and γ-tubulins” with Ken Tsui
Biophysics Seminar
October 20, 2023
2:00 PM - 3:00 PM
Location
SES 2214
Calendar
Download iCal FileTitle: “Understanding microtubule nucleation through the conformational dynamics of α, β, and γ-tubulins”
Presenter: Ken Tsui, Ma Lab, UIC Department of Biomedical Engineering
Abstract: Microtubules (MTs) are the backbone of cytoskeleton and crucial for many essential processes, such as mitosis, morphogenesis and migration. A critical step in the assembly and regulation of cellular MT network is nucleation. Most MTs nucleate from γ-tubulin ring complexes, which undergo ring closure, a complex-wide conformational change required for the ring complex to match the tube-like geometry of MT. We previously developed a model that explains how ring closure promotes nucleation: Ring complex first helps tubulins to form a sheet, then closes the sheet into tube with the help of the ring closure process. Because catastrophe (i.e. the switching from MT growth to shortening) cannot develop while sheet is open, MTs more likely grow longer and nucleate. While the predicted molecular motions during ring closure are intriguing, observation of the motions is difficult, because the structures along the paths of rare transitions elude any experimental methods, and the rates of conformational changes are beyond the timescale of molecular dynamics simulation of large proteins. Here, based on a recent breakthrough of enhanced sampling method for molecular dynamics simulation, we observed multiple conformational change pathways of tubulins. Simulations revealed machine-like molecular motions that facilitate transitions between bent, straight, and curved tubulins, and interactions at longitudinal and lateral interfaces between tubulin neighbors. These motions show how tubulins collaboratively control ring closure and initiate assembly. Our results provide a foundation for observing and understanding tubulin assembly dynamics and regulation of MT nucleation at molecular level.
Date posted
Oct 20, 2023
Date updated
Oct 20, 2023