Allosteric communication, assembly, and nucleotide hydrolysis in group II chaperonins
Abstract/Contents
- Abstract
- Protein function is dependent upon adoption of a native 3-D configuration whilst avoiding toxic conformations. Some proteins can fold spontaneously; however, the complexity of the proteome requires cellular cofactors called chaperones to ensure problematic proteins are natively folded. Chaperonins are a class of molecular chaperones that are universally conserved in all domains of life and contribute to the cellular proteostasis toolkit. They are 1-MDa complexes composed of two rings that undergo a dramatic conformational change with ATP hydrolysis to form an inner folding cavity. Chaperonins have significantly diverged in architecture, topology, and client repertoire so they are divided into two classes: group I and group II chaperonins. Group I chaperonins exist in prokarya whilst group II chaperonins are found in eukarya and archaea. All chaperonins help to orchestrate ATP-dependent client protein sequestration and refolding through encapsulation in the central folding cavity. This thesis is centered on enumerating the mechanism of a group II chaperonin found in M. Maripaludis (MmCpn), an archaeal methanogen. Biochemical and biophysical interrogation of structural moieties, chiefly the c-termini, were found to contribute to ATP hydrolysis, substrate re-folding, and complex integrity. New structural elements such as interfacial methionine fingers and electrostatic contacts were observed to undergo novel conformations, yielding new candidates for studying group II chaperonins in general. Electrostatic disruption of the c-termini allowed for dissection of multimeric states, including the long elusive single-ring species which could serve as a useful tool for understanding chaperonin biogenesis and function.
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 | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Goncalves, Kevin Olegario |
|---|---|
| Degree supervisor | Frydman, Judith |
| Thesis advisor | Frydman, Judith |
| Thesis advisor | Puglisi, Joseph D |
| Thesis advisor | Wakatsuki, Soichi |
| Degree committee member | Puglisi, Joseph D |
| Degree committee member | Wakatsuki, Soichi |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Program in Structural Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Kevin Olegario Goncalves. |
|---|---|
| Note | Submitted to the Program in Structural Biology. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/kv604nm1473 |
Access conditions
- Copyright
- © 2023 by Kevin Olegario Goncalves
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
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