The Complex Phosphorylation Patterns That Regulate the Activity of Hsp70 and Its Cochaperones

Proteins must fold into their native structure and maintain it during their lifespan to display the desired activity. To ensure proper folding and stability, and avoid generation of misfolded conformations that can be potentially cytotoxic, cells synthesize a wide variety of molecular chaperones tha...

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Detalles Bibliográficos
Autores: Velasco Carneros, Lorea, Dublang Irazabal, Leire, Moro Pérez, Fernando, Muga Villate, Arturo
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/37532
Acceso en línea:http://hdl.handle.net/10810/37532
Access Level:acceso abierto
Palabra clave:chaperones
post-translational modification
phosphorylation
human disaggregase
Hsp40
Hsp70
Hsp110
cysteine string protein
molecular chaperones
J-domain
co-chaperones
yeast Hsp110
multisite phosphorylation
conformational dynamics
legionella-pneumophila
crystal-structure
Descripción
Sumario:Proteins must fold into their native structure and maintain it during their lifespan to display the desired activity. To ensure proper folding and stability, and avoid generation of misfolded conformations that can be potentially cytotoxic, cells synthesize a wide variety of molecular chaperones that assist folding of other proteins and avoid their aggregation, which unfortunately is unavoidable under acute stress conditions. A protein machinery in metazoa, composed of representatives of the Hsp70, Hsp40, and Hsp110 chaperone families, can reactivate protein aggregates. We revised herein the phosphorylation sites found so far in members of these chaperone families and the functional consequences associated with some of them. We also discuss how phosphorylation might regulate the chaperone activity and the interaction of human Hsp70 with its accessory and client proteins. Finally, we present the information that would be necessary to decrypt the effect that post-translational modifications, and especially phosphorylation, could have on the biological activity of the Hsp70 system, known as the chaperone code.