Regulation of calcineurin through interactions at a critical substrate binding site
Abstract/Contents
- Abstract
- Cells respond to changing conditions by communicating through signal transduction pathways. Calcineurin, the Ca2+/calmodulin-activated serine/threonine protein phosphatase, mediates the cellular response to Ca2+ by regulating phosphorylation in diverse cellular contexts. Calcineurin plays key roles in development, neuronal signaling, and immunity by targeting a variety of substrates. Calcineurin substrates contain conserved motifs that bind to docking sites on the surface of the enzyme and contribute to substrate specificity. Our studies reveal that these docking surfaces are important not only for substrate recognition, but are vital for substrate engagement and positioning, and their accessibility is a requirement for functional dephosphorylation. We present research that defines one such surface, the LxVP docking pocket. Additionally, we elucidate the mechanism of inhibition by the viral protein inhibitor A238L, which inhibits calcineurin by occupying both critical substrate recognition sites while leaving the catalytic center fully accessible. Finally, we investigate the calcineurin variant CNbeta1, and discover the distinct molecular strategy by which autoinhibition and activation occurs in this isozyme. This work contributes to our knowledge of calcineurin regulation and substrate recognition, and lays the groundwork for understanding the complex signal transduction networks controlled by this important phosphatase.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Bond, Rachel Katherine Greene |
|---|---|
| Associated with | Stanford University, Department of Biology. |
| Primary advisor | Cyert, Martha S, 1958- |
| Thesis advisor | Cyert, Martha S, 1958- |
| Thesis advisor | Frydman, Judith |
| Thesis advisor | Herschlag, Daniel |
| Thesis advisor | Stearns, Tim |
| Advisor | Frydman, Judith |
| Advisor | Herschlag, Daniel |
| Advisor | Stearns, Tim |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Rachel Katherine Greene Bond. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Rachel Katherine Bond
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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