Structure and mechanism of the cation chloride cotransporter NKCC1
Abstract/Contents
- Abstract
- Ion transport is fundamental to cell homeostasis, and plays an important role in numerous physiological processes such as cell signaling and volume regulation. The cation-chloride cotransporter (CCC) family of proteins is critical for regulating volume through the careful control of sodium, potassium, and chloride transport. The intricate balance and transport of these diverse ions is responsible for maintaining cellular health, with various diseases arising when dysregulation occurs. Given their importance, CCC family members serve as major drug targets. Such proteins have been studied for decades, but structural information has been lacking due to the difficulty associated with studying membrane proteins of this size, as well as a relatively disordered N-terminus. However, in recent years technical advances in cryo-electron microscopy (cryo-EM) have made it possible to study proteins such as CCC transporters in far greater detail. Here, I describe my efforts to understand the mechanism of action of a particular member of the CCC transporter family, NKCC1. NKCC1 transports sodium, potassium, and chloride in cells throughout the body. I describe the structure of NKCC1, which shows the general fold of the CCC transporter family and the unique positioning of both cytosolic and transmembrane domains. The structure of this protein, combined with functional studies and molecular dynamics simulations allow for a deeper understanding of the CCC family of proteins. Aspects covered include the overall structure of the protein, identification of specific residues responsible for ion binding, and a proposed transport mechanism. Together, these studies shed light on this important family of proteins.
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 | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Chew, Thomas Andrew |
|---|---|
| Degree supervisor | Feng, Liang, 1976- |
| Thesis advisor | Feng, Liang, 1976- |
| Thesis advisor | Kobilka, Brian K |
| Thesis advisor | Maduke, Merritt C, 1966- |
| Degree committee member | Kobilka, Brian K |
| Degree committee member | Maduke, Merritt C, 1966- |
| Associated with | Stanford University, Biophysics Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Thomas Chew. |
|---|---|
| Note | Submitted to the Biophysics Program. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/tm218rq8189 |
Access conditions
- Copyright
- © 2021 by Thomas Andrew Chew
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