Ullah, R, Shehzad, A, Shah, MA et al. (6 more authors) (2020) C-Terminal Domain of the Human Zinc Transporter hZnT8 Is Structurally Indistinguishable from Its Disease Risk Variant (R325W). International Journal of Molecular Sciences, 21 (3). 926. ISSN 1661-6596
Abstract
The human zinc transporter 8 (hZnT8) plays important roles in the storage of insulin in the secretory vesicles of pancreatic β cells. hZnT8 consists of a transmembrane domain, with its N- and C-termini protruding into the cytoplasm. Interestingly, the exchange of arginine to tryptophan at position 325 in the C-terminal domain (CTD) increases the risk of developing type 2 diabetes mellitus (T2D). In the present study, the CTDs of hZnT8 (the wild-type (WT) and its disease risk variant (R325W)) were expressed, purified, and characterized in their native forms by biophysical techniques. The data reveal that the CTDs form tetramers which are stabilized by zinc binding, and exhibit negligible differences in their secondary structure content and zinc-binding affinities in solution. These findings provide the basis for conducting further structural studies aimed at unravelling the molecular mechanism underlying the increased susceptibility to develop T2D, which is modulated by the disease risk variant.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | human zinc transporter hZnT8; C-terminal domain; disease risk variant; biophysical characterization |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Synthetic Biology (Leed) |
Funding Information: | Funder Grant number BBSRC (Biotechnology & Biological Sciences Research Council) BBS/B/14418 |
Depositing User: | Symplectic Publications |
Date Deposited: | 22 Jan 2020 15:10 |
Last Modified: | 25 Jun 2023 22:07 |
Status: | Published |
Publisher: | MDPI |
Identification Number: | 10.3390/ijms21030926 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:155862 |