Structure and thiazide inhibition mechanism of the human sodium-chloride cotransporter
Abstract/Contents
- Abstract
- The sodium-chloride cotransporter (NCC) functions as the major salt reabsorption pathway in the distal convoluted tubule of the kidney nephron and is responsible for the fine-tuning of renal sodium excretion. Because of its importance in sodium homeostasis, NCC plays a critical role in blood pressure regulation. Thiazide diuretics, inhibitors of NCC, are therefore important first-line therapeutic agents for hypertension. Here, the work to determine the cryo-electron microscopy structures of the human NCC alone and in complex with a thiazide diuretic, polythiazide is described. I also detail my efforts to develop assays for the functional characterization of NCC, which is essential for studying its structure-function relationships. These structural and functional studies provide insights into NCC's major conformational states and transport mechanism. They also shed light on the molecular basis of how thiazide diuretics inhibit NCC and uncover several intriguing regulatory mechanisms. Together, these studies advance our understanding of the molecular mechanisms of NCC and lay the foundations to facilitate future development of next-generation NCC modulators.
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 | Lee, Chien-Ling |
|---|---|
| Degree supervisor | Feng, Liang, 1976- |
| Thesis advisor | Feng, Liang, 1976- |
| Thesis advisor | Kobilka, Brian K |
| Thesis advisor | Maduke, Merritt C, 1966- |
| Thesis advisor | Pao, Alan C |
| Degree committee member | Kobilka, Brian K |
| Degree committee member | Maduke, Merritt C, 1966- |
| Degree committee member | Pao, Alan C |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Department of Molecular and Cellular Physiology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Chien-Ling Lee. |
|---|---|
| Note | Submitted to the Department of Molecular and Cellular Physiology. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/pc759pw3800 |
Access conditions
- Copyright
- © 2023 by Chien-Ling Lee
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