Harvard Medical School
Collaborators: Jason Hon, Harvard Medical School; Mengying Zhou, Harvard Medical School; Ying Lu (advisor), Harvard Medical School
Title: A Free-Energy Landscape Approach Reveals the Global Conformational Dynamics of Proteasomal ATPases
Short Abstract: A ring of heterohexameric AAA+ ATPases on the 26S proteasome couples the chemical and mechanical cycles to achieve processive substrate unfolding and translocation during protein degradation. To understand the mechanism of how these ATPases coordinate, we developed a novel approach for delineating the nucleotide-dependent free-energy landscape (FEL) of the ATPases based on complementary structural and kinetic measurements. We used FEL to simulate the dynamics of the proteasome and found the predictions are consistent with diverse experimental observations. Our study reveals that the ATPase structure entails a unique free-energy minimum at each nucleotide state, dictating the cooperative movements of the six ATPases.
Presenter Biosketch: I am a fourth-year graduate student in the program of molecules, cells and organisms (MCO) in Harvard University, and I work in Ying Lu Lab, Dept. of Systems Biology, Harvard Medical School. I got my bachelor’s degree in the Integrated Science in 2018 from Peking University, China.
Link to Full Abstract: Fang_Rui