Single-molecule thiol-disulfide interchange
<p>Thiol-disulfide interchange occurs widely in cellular processes including redox sensing and homeostasis, protein folding, cell signalling, and the regulation of apoptosis. Nature exploits this chemistry in a highly selective manner, which is challenging to recapitulate in vitro. In this...
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Published: |
2018
|
| _version_ | 1826307584724828160 |
|---|---|
| author | Qing, Y |
| author2 | Bayley, J |
| author_facet | Bayley, J Qing, Y |
| author_sort | Qing, Y |
| collection | OXFORD |
| description | <p>Thiol-disulfide interchange occurs widely in cellular processes including redox sensing and homeostasis, protein folding, cell signalling, and the regulation of apoptosis. Nature exploits this chemistry in a highly selective manner, which is challenging to recapitulate in vitro. In this thesis, we report site selective and regioselective thioldisulfide interchange on macromolecular disulfide substrates elongated within a protein nanoreactor, where they react with cysteine thiolates presented at different locations along the length of a β strand. Numerous individual reaction events were detected by promoting the substrate turnover. For each substrate, we defined the most reactive cysteines on the β strand and which sulfur atom in the disulfide was attacked and found that the chemistry can be controlled with atomic precision.</p> <p>We further applied our control over the selectivity of thiol-disulfide interchange to the development of a molecular machine. Intrigued by technological potential, scientists have long attempted to control molecular motion. We monitor the individual 0.7-nm steps of a single molecular hopper as it moves in an electric field along a track in a nanopore controlled by a chemical ratchet based on thiol-disulfide interchange. The hopper demonstrates characteristics desired in a moving molecule: defined start- and end-points, processivity, fuel autonomy, directional motion and external control. The hopper is readily functionalized to carry cargos. For example, DNA can be ratcheted along the track in either direction, a prerequisite for nanopore sequencing.</p> |
| first_indexed | 2024-03-07T07:05:17Z |
| format | Thesis |
| id | oxford-uuid:c6ece0e7-4135-4ddc-86cf-7cc9bc0c3b0a |
| institution | University of Oxford |
| last_indexed | 2024-03-07T07:05:17Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | oxford-uuid:c6ece0e7-4135-4ddc-86cf-7cc9bc0c3b0a2022-04-25T11:46:01ZSingle-molecule thiol-disulfide interchangeThesishttp://purl.org/coar/resource_type/c_db06uuid:c6ece0e7-4135-4ddc-86cf-7cc9bc0c3b0aORA Deposit2018Qing, YBayley, J<p>Thiol-disulfide interchange occurs widely in cellular processes including redox sensing and homeostasis, protein folding, cell signalling, and the regulation of apoptosis. Nature exploits this chemistry in a highly selective manner, which is challenging to recapitulate in vitro. In this thesis, we report site selective and regioselective thioldisulfide interchange on macromolecular disulfide substrates elongated within a protein nanoreactor, where they react with cysteine thiolates presented at different locations along the length of a β strand. Numerous individual reaction events were detected by promoting the substrate turnover. For each substrate, we defined the most reactive cysteines on the β strand and which sulfur atom in the disulfide was attacked and found that the chemistry can be controlled with atomic precision.</p> <p>We further applied our control over the selectivity of thiol-disulfide interchange to the development of a molecular machine. Intrigued by technological potential, scientists have long attempted to control molecular motion. We monitor the individual 0.7-nm steps of a single molecular hopper as it moves in an electric field along a track in a nanopore controlled by a chemical ratchet based on thiol-disulfide interchange. The hopper demonstrates characteristics desired in a moving molecule: defined start- and end-points, processivity, fuel autonomy, directional motion and external control. The hopper is readily functionalized to carry cargos. For example, DNA can be ratcheted along the track in either direction, a prerequisite for nanopore sequencing.</p> |
| spellingShingle | Qing, Y Single-molecule thiol-disulfide interchange |
| title | Single-molecule thiol-disulfide interchange |
| title_full | Single-molecule thiol-disulfide interchange |
| title_fullStr | Single-molecule thiol-disulfide interchange |
| title_full_unstemmed | Single-molecule thiol-disulfide interchange |
| title_short | Single-molecule thiol-disulfide interchange |
| title_sort | single molecule thiol disulfide interchange |
| work_keys_str_mv | AT qingy singlemoleculethioldisulfideinterchange |