Regulation of yeast Snf1 (AMPK) by a polyhistidine containing pH sensing module

Summary: Cellular regulation of pH is crucial for internal biological processes and for the import and export of ions and nutrients. In the yeast Saccharomyces cerevisiae, the major proton pump (Pma1) is regulated by glucose. Glucose is also an inhibitor of the energy sensor Snf1/AMPK, which is cons...

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Main Authors: Kobi J. Simpson-Lavy, Martin Kupiec
Format: Article
Language:English
Published: Elsevier 2022-10-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004222013554
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author Kobi J. Simpson-Lavy
Martin Kupiec
author_facet Kobi J. Simpson-Lavy
Martin Kupiec
author_sort Kobi J. Simpson-Lavy
collection DOAJ
description Summary: Cellular regulation of pH is crucial for internal biological processes and for the import and export of ions and nutrients. In the yeast Saccharomyces cerevisiae, the major proton pump (Pma1) is regulated by glucose. Glucose is also an inhibitor of the energy sensor Snf1/AMPK, which is conserved in all eukaryotes. Here, we demonstrate that a poly-histidine (polyHIS) tract in the pre-kinase region (PKR) of Snf1 functions as a pH-sensing module (PSM) and regulates Snf1 activity. This regulation is independent from, and unaffected by, phosphorylation at T210, the major regulatory control of Snf1, but is controlled by the Pma1 plasma-membrane proton pump. By examining the PKR from additional yeast species, and by varying the number of histidines in the PKR, we determined that the polyHIS functions progressively. This regulation mechanism links the activity of a key enzyme with the metabolic status of the cell at any given moment.
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spelling doaj.art-313810acec7647d9b4b58f3e55f2b4b22022-12-22T04:04:29ZengElsevieriScience2589-00422022-10-012510105083Regulation of yeast Snf1 (AMPK) by a polyhistidine containing pH sensing moduleKobi J. Simpson-Lavy0Martin Kupiec1The Shmunis School of Biomedicine & Cancer Research, Tel Aviv University, Ramat Aviv 69978, IsraelThe Shmunis School of Biomedicine & Cancer Research, Tel Aviv University, Ramat Aviv 69978, Israel; Corresponding authorSummary: Cellular regulation of pH is crucial for internal biological processes and for the import and export of ions and nutrients. In the yeast Saccharomyces cerevisiae, the major proton pump (Pma1) is regulated by glucose. Glucose is also an inhibitor of the energy sensor Snf1/AMPK, which is conserved in all eukaryotes. Here, we demonstrate that a poly-histidine (polyHIS) tract in the pre-kinase region (PKR) of Snf1 functions as a pH-sensing module (PSM) and regulates Snf1 activity. This regulation is independent from, and unaffected by, phosphorylation at T210, the major regulatory control of Snf1, but is controlled by the Pma1 plasma-membrane proton pump. By examining the PKR from additional yeast species, and by varying the number of histidines in the PKR, we determined that the polyHIS functions progressively. This regulation mechanism links the activity of a key enzyme with the metabolic status of the cell at any given moment.http://www.sciencedirect.com/science/article/pii/S2589004222013554Biological sciencesbiochemistrymolecular biology
spellingShingle Kobi J. Simpson-Lavy
Martin Kupiec
Regulation of yeast Snf1 (AMPK) by a polyhistidine containing pH sensing module
iScience
Biological sciences
biochemistry
molecular biology
title Regulation of yeast Snf1 (AMPK) by a polyhistidine containing pH sensing module
title_full Regulation of yeast Snf1 (AMPK) by a polyhistidine containing pH sensing module
title_fullStr Regulation of yeast Snf1 (AMPK) by a polyhistidine containing pH sensing module
title_full_unstemmed Regulation of yeast Snf1 (AMPK) by a polyhistidine containing pH sensing module
title_short Regulation of yeast Snf1 (AMPK) by a polyhistidine containing pH sensing module
title_sort regulation of yeast snf1 ampk by a polyhistidine containing ph sensing module
topic Biological sciences
biochemistry
molecular biology
url http://www.sciencedirect.com/science/article/pii/S2589004222013554
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