Assembly and allostery in group II chaperonins
Abstract/Contents
- Abstract
- Proteins must achieve their native conformations in order to function and avoid aberrant interactions within the cell. The folded state is formed rapidly for proteins with simple topologies. However, the folding of many large proteins with complex folds is assisted by the diverse array of molecular chaperones. The chaperonins are a unique class of essential protein chaperones found in all domains of life. These complexes are comprised of two 7-9 membered rings that undergo dramatic conforma- tional changes upon ATP binding and hydrolysis. Two classes of chaperonins exist, termed group I and group II. Group I chaperonins exist in bacteria and endosymbiotic organelles, while group II chaperonins are found in all eukaryotes and archaea. Both families promote the folding of substrates in an ATP dependent manner by encapsulating them within discrete central chambers. This thesis focuses on detailing the mechanism of a model group II chaperonin from the archaea Methanococcus maripaludis. Work was performed to define the native folding substrates of the complex as well as to detail the cooperative mechanism that controls all group II chaperonin cycling. A key allosteric interface was identified using a mathematical approach that predicts functionally important residues based on patterns of covariation found in multiple sequence alignments of a protein. Biochemical dissection of mutations at this interface reveal that the chaperonins have evolved to be less cooperative than attainable. Early evidence will be presented that suggests the N- and C-terminal tails of the chaperonin likely serve as coordinators of nucleotide cycling.
Description
Type of resource | text |
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Form | electronic; electronic resource; remote |
Extent | 1 online resource. |
Publication date | 2017 |
Issuance | monographic |
Language | English |
Creators/Contributors
Associated with | Lopez, Thomas Steven | |
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Associated with | Stanford University, Department of Biology. | |
Primary advisor | Frydman, Judith | |
Thesis advisor | Frydman, Judith | |
Thesis advisor | Cyert, Martha S, 1958- | |
Thesis advisor | Wandless, Thomas | |
Thesis advisor | Weis, William I | |
Advisor | Cyert, Martha S, 1958- | |
Advisor | Wandless, Thomas | |
Advisor | Weis, William I |
Subjects
Genre | Theses |
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Bibliographic information
Statement of responsibility | Thomas Steven Lopez. |
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Note | Submitted to the Department of Biology. |
Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Thomas Steven Lopez
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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