A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypes
The modifications occurring to CaaX proteins have largely been established using few reporter molecules (e.g. Ras, yeast a-factor mating pheromone). These proteins undergo three coordinated COOH-terminal events: isoprenylation of the cysteine, proteolytic removal of aaX, and COOH-terminal methylatio...
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doaj-e741b9c87aa243a4b82d9206308164c12021-05-05T00:31:44ZengeLife Sciences Publications LtdeLife2050-084X2016-08-01510.7554/eLife.15899A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypesEmily R Hildebrandt0Michael Cheng1Peng Zhao2June H Kim3Lance Wells4https://orcid.org/0000-0003-4956-5363Walter K Schmidt5https://orcid.org/0000-0002-3359-3434Department of Biochemistry and Molecular Biology, University of Georgia, Athens, United StatesDepartment of Biochemistry and Molecular Biology, University of Georgia, Athens, United StatesDepartment of Biochemistry and Molecular Biology, University of Georgia, Athens, United StatesDepartment of Biochemistry and Molecular Biology, University of Georgia, Athens, United StatesDepartment of Biochemistry and Molecular Biology, University of Georgia, Athens, United StatesDepartment of Biochemistry and Molecular Biology, University of Georgia, Athens, United StatesThe modifications occurring to CaaX proteins have largely been established using few reporter molecules (e.g. Ras, yeast a-factor mating pheromone). These proteins undergo three coordinated COOH-terminal events: isoprenylation of the cysteine, proteolytic removal of aaX, and COOH-terminal methylation. Here, we investigated the coupling of these modifications in the context of the yeast Ydj1p chaperone. We provide genetic, biochemical, and biophysical evidence that the Ydj1p CaaX motif is isoprenylated but not cleaved and carboxylmethylated. Moreover, we demonstrate that Ydj1p-dependent thermotolerance and Ydj1p localization are perturbed when alternative CaaX motifs are transplanted onto Ydj1p. The abnormal phenotypes revert to normal when post-isoprenylation events are genetically interrupted. Our findings indicate that proper Ydj1p function requires an isoprenylatable CaaX motif that is resistant to post-isoprenylation events. These results expand on the complexity of protein isoprenylation and highlight the impact of post-isoprenylation events in regulating the function of Ydj1p and perhaps other CaaX proteins.https://elifesciences.org/articles/15899CaaXHSP40isoprenylationchaperonethermotolerance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Emily R Hildebrandt Michael Cheng Peng Zhao June H Kim Lance Wells Walter K Schmidt |
spellingShingle |
Emily R Hildebrandt Michael Cheng Peng Zhao June H Kim Lance Wells Walter K Schmidt A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypes eLife CaaX HSP40 isoprenylation chaperone thermotolerance |
author_facet |
Emily R Hildebrandt Michael Cheng Peng Zhao June H Kim Lance Wells Walter K Schmidt |
author_sort |
Emily R Hildebrandt |
title |
A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypes |
title_short |
A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypes |
title_full |
A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypes |
title_fullStr |
A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypes |
title_full_unstemmed |
A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypes |
title_sort |
shunt pathway limits the caax processing of hsp40 ydj1p and regulates ydj1p-dependent phenotypes |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2016-08-01 |
description |
The modifications occurring to CaaX proteins have largely been established using few reporter molecules (e.g. Ras, yeast a-factor mating pheromone). These proteins undergo three coordinated COOH-terminal events: isoprenylation of the cysteine, proteolytic removal of aaX, and COOH-terminal methylation. Here, we investigated the coupling of these modifications in the context of the yeast Ydj1p chaperone. We provide genetic, biochemical, and biophysical evidence that the Ydj1p CaaX motif is isoprenylated but not cleaved and carboxylmethylated. Moreover, we demonstrate that Ydj1p-dependent thermotolerance and Ydj1p localization are perturbed when alternative CaaX motifs are transplanted onto Ydj1p. The abnormal phenotypes revert to normal when post-isoprenylation events are genetically interrupted. Our findings indicate that proper Ydj1p function requires an isoprenylatable CaaX motif that is resistant to post-isoprenylation events. These results expand on the complexity of protein isoprenylation and highlight the impact of post-isoprenylation events in regulating the function of Ydj1p and perhaps other CaaX proteins. |
topic |
CaaX HSP40 isoprenylation chaperone thermotolerance |
url |
https://elifesciences.org/articles/15899 |
work_keys_str_mv |
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