Abstract

ATP-independent chaperones like trigger factor are generally assumed to play passive roles in protein folding by acting as holding chaperones. Here we show that trigger factor plays a more active role. Consistent with a role as an aggregation inhibiting chaperone, we find that trigger factor rapidly binds to partially folded glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and prevents it from non-productive self-association by shielding oligomeric interfaces. In the traditional view of holding chaperone action, trigger factor would then be expected to transfer its client to a chaperone foldase system for complete folding. Unexpectedly, we noticed that GAPDH folds into a monomeric but otherwise rather native-like intermediate state while trigger factor-bound. Upon release from trigger factor, the mostly folded monomeric GAPDH rapidly self-associates into its native tetramer and acquires enzymatic activity without needing additional folding factors. The mechanism we propose here for trigger factor bridges the holding and folding activities of chaperone function.

Using Guanidium HCl denatured glyceraldehyde 3-phosphate dehydrogenase (GAPDH), the authors provide in vitro evidence for the active involvement of the trigger factor (TF) in promoting the native folding of pre-unfolded client proteins, by preventing non-productive self-associations (misfolding) and by shielding oligomeric interfaces from aggregation.

Details

Title
Trigger factor both holds and folds its client proteins
Author
Wu, Kevin 1   VIAFID ORCID Logo  ; Minshull, Thomas C. 2 ; Radford, Sheena E. 2   VIAFID ORCID Logo  ; Calabrese, Antonio N. 2   VIAFID ORCID Logo  ; Bardwell, James C. A. 1   VIAFID ORCID Logo 

 University of Michigan, Department of Molecular, Cellular, and Developmental Biology and Howard Hughes Medical Institute, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
 University of Leeds, Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, Leeds, UK (GRID:grid.9909.9) (ISNI:0000 0004 1936 8403) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2690022786
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.