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The zinc transporter SLC39A7 (ZIP7) harbours a highly-conserved histidinerich N-terminal region that potentially contributes to zinc homeostasis in the endoplasmic reticulum

journal contribution
posted on 2023-05-19, 19:36 authored by John Adulcikas, Norouzi, S, Bretag, L, Sukhwinder SohalSukhwinder Sohal, Stephen MyersStephen Myers
The zinc transporter SLC39A7 (ZIP7)1 is a resident endoplasmic reticulum (ER) protein that is involved in controlling the release of zinc from this organelle into the cytosol. Subsequently, zinc plays a major role in processes that preserve cellular homeostasis. The ER contains a high concentration of zinc, and under normal physiological responses, maintains ER function. Disturbances in the concentration and distribution of zinc in the ER leads to abnormal processes that typify many disease states. ZIP7 is protective against ER stress and is a critical ‘gate-keeper’ of zinc release from the ER during processes that require cellular maintenance. However, it is not known how ZIP7 achieves this protective activity while maintaining cellular function. Bioinformatics analysis was utilised to determine the relationship between ZIP7 and other zinc transporters across humans and the animal and plant kingdom to determine the structure of this transporter in binding zinc in the ER. Analysis of the amino acid sequence of ZIP7 revealed several potential histidine binding sites for zinc in the N-terminal region that were significantly different in comparison to the other members of this family. Moreover, this histidine-rich region in the N-terminal of ZIP7 was highly conserved across the animal and plant kingdom. Accordingly, the highly conserved histidine-rich region in the N-termini of ZIP7 across the animal and plant kingdom suggests that this domain has critical function(s). We hypothesise that ER-localized ZIP7 can potentially sequester zinc to these histidine-rich regions and therefore provides a mechanism that is protective of this cellular structure.

Funding

Clifford Craig Foundation

History

Publication title

Computers in Biology and Medicine

Volume

100

Pagination

196-202

ISSN

0010-4825

Department/School

College Office - College of Health and Medicine

Publisher

Pergamon-Elsevier Science Ltd

Place of publication

The Boulevard, Langford Lane, Kidlington, Oxford, England, Ox5 1Gb

Rights statement

Copyright 2018 Published by Elsevier Ltd.

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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