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Structure of the Yeast Cell Wall Integrity Sensor Wsc1 Reveals an Essential Role of Surface-Exposed Aromatic Clusters

In the yeast Saccharomyces cerevisiae and other ascomycetes, the maintenance of cell wall integrity is governed by a family of plasma-membrane spanning sensors that include the Wsc-type proteins. These cell wall proteins apparently sense stress-induced mechanical forces at the cell surface and targe...

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Autores principales: Schöppner, Philipp, Lutz, Anne Pia, Lutterbach, Bernard Johannes, Brückner, Stefan, Essen, Lars-Oliver, Mösch, Hans-Ulrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024836/
https://www.ncbi.nlm.nih.gov/pubmed/35448610
http://dx.doi.org/10.3390/jof8040379
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author Schöppner, Philipp
Lutz, Anne Pia
Lutterbach, Bernard Johannes
Brückner, Stefan
Essen, Lars-Oliver
Mösch, Hans-Ulrich
author_facet Schöppner, Philipp
Lutz, Anne Pia
Lutterbach, Bernard Johannes
Brückner, Stefan
Essen, Lars-Oliver
Mösch, Hans-Ulrich
author_sort Schöppner, Philipp
collection PubMed
description In the yeast Saccharomyces cerevisiae and other ascomycetes, the maintenance of cell wall integrity is governed by a family of plasma-membrane spanning sensors that include the Wsc-type proteins. These cell wall proteins apparently sense stress-induced mechanical forces at the cell surface and target the cell wall integrity (CWI) signaling pathway, but the structural base for their sensor function is yet unknown. Here, we solved a high-resolution crystal structure of the extracellular cysteine-rich domain (CRD) of yeast Wsc1, which shows the characteristic PAN/Apple domain fold with two of the four Wsc1 disulfide bridges being conserved in other PAN domain cores. Given the general function of PAN domains in mediating protein–protein and protein–carbohydrate interactions, this finding underpins the importance of Wsc domains in conferring sensing and localization functions. Our Wsc1 CRD structure reveals an unusually high number of surface-exposed aromatic residues that are conserved in other fungal CRDs, and can be arranged into three solvent-exposed clusters. Mutational analysis demonstrates that two of the aromatic clusters are required for conferring S. cerevisiae Wsc1-dependent resistance to the glucan synthase inhibitor caspofungin, and the chitin-binding agents Congo red and Calcofluor white. These findings suggest an essential role of surface-exposed aromatic clusters in fungal Wsc-type sensors that might include an involvement in stress-induced sensor-clustering required to elicit appropriate cellular responses via the downstream CWI pathway.
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spelling pubmed-90248362022-04-23 Structure of the Yeast Cell Wall Integrity Sensor Wsc1 Reveals an Essential Role of Surface-Exposed Aromatic Clusters Schöppner, Philipp Lutz, Anne Pia Lutterbach, Bernard Johannes Brückner, Stefan Essen, Lars-Oliver Mösch, Hans-Ulrich J Fungi (Basel) Article In the yeast Saccharomyces cerevisiae and other ascomycetes, the maintenance of cell wall integrity is governed by a family of plasma-membrane spanning sensors that include the Wsc-type proteins. These cell wall proteins apparently sense stress-induced mechanical forces at the cell surface and target the cell wall integrity (CWI) signaling pathway, but the structural base for their sensor function is yet unknown. Here, we solved a high-resolution crystal structure of the extracellular cysteine-rich domain (CRD) of yeast Wsc1, which shows the characteristic PAN/Apple domain fold with two of the four Wsc1 disulfide bridges being conserved in other PAN domain cores. Given the general function of PAN domains in mediating protein–protein and protein–carbohydrate interactions, this finding underpins the importance of Wsc domains in conferring sensing and localization functions. Our Wsc1 CRD structure reveals an unusually high number of surface-exposed aromatic residues that are conserved in other fungal CRDs, and can be arranged into three solvent-exposed clusters. Mutational analysis demonstrates that two of the aromatic clusters are required for conferring S. cerevisiae Wsc1-dependent resistance to the glucan synthase inhibitor caspofungin, and the chitin-binding agents Congo red and Calcofluor white. These findings suggest an essential role of surface-exposed aromatic clusters in fungal Wsc-type sensors that might include an involvement in stress-induced sensor-clustering required to elicit appropriate cellular responses via the downstream CWI pathway. MDPI 2022-04-08 /pmc/articles/PMC9024836/ /pubmed/35448610 http://dx.doi.org/10.3390/jof8040379 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schöppner, Philipp
Lutz, Anne Pia
Lutterbach, Bernard Johannes
Brückner, Stefan
Essen, Lars-Oliver
Mösch, Hans-Ulrich
Structure of the Yeast Cell Wall Integrity Sensor Wsc1 Reveals an Essential Role of Surface-Exposed Aromatic Clusters
title Structure of the Yeast Cell Wall Integrity Sensor Wsc1 Reveals an Essential Role of Surface-Exposed Aromatic Clusters
title_full Structure of the Yeast Cell Wall Integrity Sensor Wsc1 Reveals an Essential Role of Surface-Exposed Aromatic Clusters
title_fullStr Structure of the Yeast Cell Wall Integrity Sensor Wsc1 Reveals an Essential Role of Surface-Exposed Aromatic Clusters
title_full_unstemmed Structure of the Yeast Cell Wall Integrity Sensor Wsc1 Reveals an Essential Role of Surface-Exposed Aromatic Clusters
title_short Structure of the Yeast Cell Wall Integrity Sensor Wsc1 Reveals an Essential Role of Surface-Exposed Aromatic Clusters
title_sort structure of the yeast cell wall integrity sensor wsc1 reveals an essential role of surface-exposed aromatic clusters
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024836/
https://www.ncbi.nlm.nih.gov/pubmed/35448610
http://dx.doi.org/10.3390/jof8040379
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