Structural studies of human mitochondrial LonP1 and cytosolic prefoldin involved in protein homeostasis

Mohammed, Inayathulla. Structural studies of human mitochondrial LonP1 and cytosolic prefoldin involved in protein homeostasis. 2020, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: https://edoc.unibas.ch/88019/

Downloads: Statistics Overview


The mitochondrial Lon protease homolog (LonP1) hexamer controls mitochondrial health by digesting proteins from the mitochondrial matrix that are damaged or must be removed. Understanding how it is regulated requires characterizing its mechanism. Here, we show how human LonP1 functions, based on eight different conformational states that we determined by cryo-EM with a resolution locally extending to 3.6 Å for the best ordered states. LonP1 has a poorly ordered N-terminal part with apparent threefold symmetry, which apparently binds substrate protein and feeds it into its AAA+ unfoldase core. This translocates the extended substrate protein into a proteolytic cavity, in which we report an additional, previously unidentified Thr-type proteolytic center. Threefold rocking movements of the flexible N-terminal assembly likely assist thermal unfolding of the substrate protein. Our data suggest LonP1 may function as a sixfold cyclical Brownian ratchet controlled by ATP hydrolysis.
Advisors:Abrahams, Jan Pieter
Committee Members:Stahlberg, Henning
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Nano-diffraction of Biological Specimen (Abrahams)
UniBasel Contributors:Abrahams, Jan Pieter and Stahlberg, Henning
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:14638
Thesis status:Complete
Number of Pages:152
Identification Number:
  • urn: urn:nbn:ch:bel-bau-diss146382
edoc DOI:
Last Modified:18 Mar 2022 05:30
Deposited On:17 Mar 2022 16:00

Repository Staff Only: item control page