Cryo-EM study of ATP induced conformational heterogeneity in archaeal chaperonin mmCpn
Abstract/Contents
- Abstract
- Proteins must fold into their correct three-dimensional conformations to function properly. Aberrant folding has been linked to a rapidly expanding list of pathologies, including Alzheimer's disease (AD) and Parkinson's disease (PD). However, the vast majority of cellular proteins are unable to reach their native state spontaneously. The correct folding of these proteins requires the assistance of a complex cellular machinery of proteins known as molecular chaperones. Among the chaperones, chaperonin is a highly conserved subgroup that consists of two stacked seven- to nine-membered rings. These chaperonins bind nonnative polypeptides in their central cavity and use energy from ATP to mediate the polypeptide folding. So far, ATP induced conformational changes in chaperonins are considered to be coordinated in time and space by complex allosteric regulation. However, the current models employed to describe allostery in chaperonin do not distinguish allostery in ATP binding from that in ATP hydrolysis. Here I use cryo-EM to study the ATP occupancy and distribution in each ring of the archaea Methanococcus maripaludis mmCpn chaperonin complex. By exploring the nucleotide distribution in hundreds of thousands of mmCpn subunits, I find that ATP binding to chaperonin mmCpn is statistically random both within the ring and across the ring. The quarternary structure of mmCpn differs from particle to particle and the lid closing of the two rings is found to be uncorrelated to each other. Our observation of a high subunit conformational and compositional heterogeneity in each ring of mmCpn complex suggests that intra-ring subunit conformational change is non-concerted and the existence of intermediate states may help explain chaperonin's ability to fold very large protein substrates
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Zhao, Yanyan |
|---|---|
| Degree supervisor | Chiu, Wah |
| Thesis advisor | Chiu, Wah |
| Thesis advisor | Frydman, Judith |
| Thesis advisor | Wakatsuki, Soichi |
| Degree committee member | Frydman, Judith |
| Degree committee member | Wakatsuki, Soichi |
| Associated with | Stanford University, Biophysics Program. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Yanyan Zhao |
|---|---|
| Note | Submitted to the Biophysics Program |
| Thesis | Thesis Ph.D. Stanford University 2020 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Yanyan Zhao
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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