Web of Science: 2 cites, Scopus: 2 cites, Google Scholar: cites
Comparative Analysis of Type 1 and Type Z Protein Phosphatases Reveals D615 as a Key Residue for Ppz1 Regulation
Casamayor Gracia, Antonio (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Velázquez, Diego (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Santolaria, Carlos (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Albacar, Marcel (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Rasmussen, Morten I. (University of Southern Denmark. Department of Biochemistry and Molecular Biology)
Højrup, Peter (University of Southern Denmark. Department of Biochemistry and Molecular Biology)
Ariño Carmona, Joaquín (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Data: 2022
Resum: Type 1 Ser/Thr protein phosphatases are represented in all fungi by two enzymes, the ubiquitous PP1, with a conserved catalytic polypeptide (PP1c) and numerous regulatory subunits, and PPZ, with a C-terminal catalytic domain related to PP1c and a variable N-terminal extension. Current evidence indicates that, although PP1 and PPZ enzymes might share some cellular targets and regulatory subunits, their functions are quite separated, and they have individual regulation. We explored the structures of PP1c and PPZ across 57 fungal species to identify those features that (1) are distinctive among these enzymes and (2) have been preserved through evolution. PP1c enzymes are more conserved than PPZs. Still, we identified 26 residues in the PP1 and PPZ catalytic moieties that are specific for each kind of phosphatase. In some cases, these differences likely affect the distribution of charges in the surface of the protein. In many fungi, Hal3 is a specific inhibitor of the PPZ phosphatases, although the basis for the interaction of these proteins is still obscure. By in vivo co-purification of the catalytic domain of ScPpz1 and ScHal3, followed by chemical cross-linking and MS analysis, we identified a likely Hal3-interacting region in ScPpz1 characterized by two major and conserved differences, D566 and D615 in ScPpz1, which correspond to K210 and K259 in ScPP1c (Glc7). Functional analysis showed that changing D615 to K renders Ppz1 refractory to Hal3 inhibition. Since ScHal3 does not regulate Glc7 but it inhibits all fungal PPZ tested so far, this conserved D residue could be pivotal for the differential regulation of both enzymes in fungi.
Ajuts: Agencia Estatal de Investigación BFU2017-82574-P
Drets: 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
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: Protein phosphatase ; Ppz1 ; PP1c ; Sequence comparisons ; Cross-linking proteomics ; Enzyme inhibition ; Fungi
Publicat a: International journal of molecular sciences, Vol. 23, Issue 3 (January 2022) , art. 1327, ISSN 1422-0067

Adreça alternativa: https://doi.org/10.3390/ijms23031327
DOI: 10.3390/ijms23031327
PMID: 35163251


18 p, 3.1 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Articles de recerca
Articles > Articles publicats

 Registre creat el 2022-02-27, darrera modificació el 2022-07-02



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