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The inhibitory mechanism of Hal3 on the yeast Ppz1 phosphatase : A mutagenesis analysis
Molero Merinero, Cristina (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Casado Vázquez, Carlos (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Ariño Carmona, Joaquín (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)

Fecha: 2017
Resumen: The Ser/Thr protein phosphatase (PPase) Ppz1 is an enzyme related to the ubiquitous type-1 PPases (PP1c) but found only in fungi. It is regulated by an inhibitory subunit, Hal3, which binds to its catalytic domain. Overexpression of Ppz1 is highly toxic for yeast cells, so its de-regulation has been proposed as a target for novel antifungal therapies. While modulation of PP1c by its many regulatory subunits has been extensively characterized, the manner by which Hal3 controls Ppz1 remains unknown. We have used error-prone PCR mutagenesis to construct a library of Ppz1 variants and developed a functional assay to identify mutations afecting the binding or/and the inhibitory capacity of Hal3. We have characterized diverse Ppz1 mutated versions in vivo and in vitro and found that, although they were clearly refractory to Hal3 inhibition, none of them exhibited signifcant reduction in Hal3 binding. Mapping the mutations strengthened the notion that Hal3 does not interact with Ppz1 through its RVxF-like motif (found in most PP1c regulators). In contrast, the most relevant mutations mapped to a conserved α-helix region used by mammalian Inhibitor-2 to regulate PP1c. Therefore, modulation of PP1c and Ppz1 by their subunits likely difers, but could share some structural features.
Derechos: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Lengua: Anglès
Documento: article ; recerca ; publishedVersion
Publicado en: Scientific reports, Vol. 7 (2017) , art. 8819, ISSN 2045-2322

DOI: 10.1038/s41598-017-09360-5
PMID: 28821821

14 p, 2.9 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Instituto de Biotecnología y de Biomedicina (IBB)
Artículos > Artículos de investigación
Artículos > Artículos publicados

 Registro creado el 2019-06-18, última modificación el 2020-08-08

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