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Computational and cellular exploration of the protein-protein interaction between Vibrio fischeri STAS domain protein SypA and serine kinase SypE

Anti-sigma factor antagonists SpoIIAA and RsbV from Bacillus subtilis are the archetypes for single-domain STAS proteins in bacteria. The structures and mechanisms of these proteins along with their cognate anti-sigma factors have been well studied. SpoIIAA and RsbV utilize a partner-switching mecha...

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Autores principales: Milton, Morgan E., Visick, Karen L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120452/
https://www.ncbi.nlm.nih.gov/pubmed/37091830
http://dx.doi.org/10.1080/19420889.2023.2203626
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author Milton, Morgan E.
Visick, Karen L.
author_facet Milton, Morgan E.
Visick, Karen L.
author_sort Milton, Morgan E.
collection PubMed
description Anti-sigma factor antagonists SpoIIAA and RsbV from Bacillus subtilis are the archetypes for single-domain STAS proteins in bacteria. The structures and mechanisms of these proteins along with their cognate anti-sigma factors have been well studied. SpoIIAA and RsbV utilize a partner-switching mechanism to regulate gene expression through protein-protein interactions to control the activity of their downstream anti-sigma factor partners. The Vibrio fischeri STAS domain protein SypA is also proposed to employ a partner-switching mechanism with its partner SypE, a serine kinase/phosphatase that controls SypA’s phosphorylation state. However, this regulation appears opposite to the canonical pathway, with SypA being the more downstream component rather than SypE. Here we explore the commonalities and differences between SypA and the canonical single-domain STAS proteins SpoIIAA and RsbV. We use a combination of AlphaFold 2 structure predictions and computational modeling to investigate the SypA-SypE binding interface. We then test a subset of our predictions in V.fischeri by generating and expressing SypA variants. Our findings suggest that, while SypA shares many sequence and structural traits with anti-sigma factor antagonist STAS domain proteins, there are significant differences that may account for SypA’s distinct regulatory output.
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spelling pubmed-101204522023-04-22 Computational and cellular exploration of the protein-protein interaction between Vibrio fischeri STAS domain protein SypA and serine kinase SypE Milton, Morgan E. Visick, Karen L. Commun Integr Biol Short Communication Anti-sigma factor antagonists SpoIIAA and RsbV from Bacillus subtilis are the archetypes for single-domain STAS proteins in bacteria. The structures and mechanisms of these proteins along with their cognate anti-sigma factors have been well studied. SpoIIAA and RsbV utilize a partner-switching mechanism to regulate gene expression through protein-protein interactions to control the activity of their downstream anti-sigma factor partners. The Vibrio fischeri STAS domain protein SypA is also proposed to employ a partner-switching mechanism with its partner SypE, a serine kinase/phosphatase that controls SypA’s phosphorylation state. However, this regulation appears opposite to the canonical pathway, with SypA being the more downstream component rather than SypE. Here we explore the commonalities and differences between SypA and the canonical single-domain STAS proteins SpoIIAA and RsbV. We use a combination of AlphaFold 2 structure predictions and computational modeling to investigate the SypA-SypE binding interface. We then test a subset of our predictions in V.fischeri by generating and expressing SypA variants. Our findings suggest that, while SypA shares many sequence and structural traits with anti-sigma factor antagonist STAS domain proteins, there are significant differences that may account for SypA’s distinct regulatory output. Taylor & Francis 2023-04-20 /pmc/articles/PMC10120452/ /pubmed/37091830 http://dx.doi.org/10.1080/19420889.2023.2203626 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Short Communication
Milton, Morgan E.
Visick, Karen L.
Computational and cellular exploration of the protein-protein interaction between Vibrio fischeri STAS domain protein SypA and serine kinase SypE
title Computational and cellular exploration of the protein-protein interaction between Vibrio fischeri STAS domain protein SypA and serine kinase SypE
title_full Computational and cellular exploration of the protein-protein interaction between Vibrio fischeri STAS domain protein SypA and serine kinase SypE
title_fullStr Computational and cellular exploration of the protein-protein interaction between Vibrio fischeri STAS domain protein SypA and serine kinase SypE
title_full_unstemmed Computational and cellular exploration of the protein-protein interaction between Vibrio fischeri STAS domain protein SypA and serine kinase SypE
title_short Computational and cellular exploration of the protein-protein interaction between Vibrio fischeri STAS domain protein SypA and serine kinase SypE
title_sort computational and cellular exploration of the protein-protein interaction between vibrio fischeri stas domain protein sypa and serine kinase sype
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120452/
https://www.ncbi.nlm.nih.gov/pubmed/37091830
http://dx.doi.org/10.1080/19420889.2023.2203626
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