Predicting PY motif-mediated protein-protein interactions in the Nedd4 family of ubiquitin ligases.

The Nedd4 family contains several structurally related but functionally distinct HECT-type ubiquitin ligases. The members of the Nedd4 family are known to recognize substrates through their multiple WW domains, which recognize PY motifs (PPxY, LPxY) or phospho-threonine or phospho-serine residues. T...

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Autores principales:	A Katherine Hatstat, Michael D Pupi, Dewey G McCafferty
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe4dfcb0bce545759a11255ebe61711e
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spelling	oai:doaj.org-article:fe4dfcb0bce545759a11255ebe61711e2021-12-02T20:13:44ZPredicting PY motif-mediated protein-protein interactions in the Nedd4 family of ubiquitin ligases.1932-620310.1371/journal.pone.0258315https://doaj.org/article/fe4dfcb0bce545759a11255ebe61711e2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258315https://doaj.org/toc/1932-6203The Nedd4 family contains several structurally related but functionally distinct HECT-type ubiquitin ligases. The members of the Nedd4 family are known to recognize substrates through their multiple WW domains, which recognize PY motifs (PPxY, LPxY) or phospho-threonine or phospho-serine residues. To better understand protein interactor recognition mechanisms across the Nedd4 family, we report the development and implementation of a python-based tool, PxYFinder, to identify PY motifs in the primary sequences of previously identified interactors of Nedd4 and related ligases. Using PxYFinder, we find that, on average, half of Nedd4 family interactions are likely PY-motif mediated. Further, we find that PPxY motifs are more prevalent than LPxY motifs and are more likely to occur in proline-rich regions and that PPxY regions are more disordered on average relative to LPxY-containing regions. Informed by consensus sequences for PY motifs across the Nedd4 interactome, we rationally designed a focused peptide library and employed a computational screen, revealing sequence- and biomolecular interaction-dependent determinants of WW-domain/PY-motif interactions. Cumulatively, our efforts provide a new bioinformatic tool and expand our understanding of sequence and structural factors that contribute to PY-motif mediated interactor recognition across the Nedd4 family.A Katherine HatstatMichael D PupiDewey G McCaffertyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258315 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q A Katherine Hatstat Michael D Pupi Dewey G McCafferty Predicting PY motif-mediated protein-protein interactions in the Nedd4 family of ubiquitin ligases.
description	The Nedd4 family contains several structurally related but functionally distinct HECT-type ubiquitin ligases. The members of the Nedd4 family are known to recognize substrates through their multiple WW domains, which recognize PY motifs (PPxY, LPxY) or phospho-threonine or phospho-serine residues. To better understand protein interactor recognition mechanisms across the Nedd4 family, we report the development and implementation of a python-based tool, PxYFinder, to identify PY motifs in the primary sequences of previously identified interactors of Nedd4 and related ligases. Using PxYFinder, we find that, on average, half of Nedd4 family interactions are likely PY-motif mediated. Further, we find that PPxY motifs are more prevalent than LPxY motifs and are more likely to occur in proline-rich regions and that PPxY regions are more disordered on average relative to LPxY-containing regions. Informed by consensus sequences for PY motifs across the Nedd4 interactome, we rationally designed a focused peptide library and employed a computational screen, revealing sequence- and biomolecular interaction-dependent determinants of WW-domain/PY-motif interactions. Cumulatively, our efforts provide a new bioinformatic tool and expand our understanding of sequence and structural factors that contribute to PY-motif mediated interactor recognition across the Nedd4 family.
format	article
author	A Katherine Hatstat Michael D Pupi Dewey G McCafferty
author_facet	A Katherine Hatstat Michael D Pupi Dewey G McCafferty
author_sort	A Katherine Hatstat
title	Predicting PY motif-mediated protein-protein interactions in the Nedd4 family of ubiquitin ligases.
title_short	Predicting PY motif-mediated protein-protein interactions in the Nedd4 family of ubiquitin ligases.
title_full	Predicting PY motif-mediated protein-protein interactions in the Nedd4 family of ubiquitin ligases.
title_fullStr	Predicting PY motif-mediated protein-protein interactions in the Nedd4 family of ubiquitin ligases.
title_full_unstemmed	Predicting PY motif-mediated protein-protein interactions in the Nedd4 family of ubiquitin ligases.
title_sort	predicting py motif-mediated protein-protein interactions in the nedd4 family of ubiquitin ligases.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/fe4dfcb0bce545759a11255ebe61711e
work_keys_str_mv	AT akatherinehatstat predictingpymotifmediatedproteinproteininteractionsinthenedd4familyofubiquitinligases AT michaeldpupi predictingpymotifmediatedproteinproteininteractionsinthenedd4familyofubiquitinligases AT deweygmccafferty predictingpymotifmediatedproteinproteininteractionsinthenedd4familyofubiquitinligases
_version_	1718374743438000128

Predicting PY motif-mediated protein-protein interactions in the Nedd4 family of ubiquitin ligases.

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