Human GRP78 affinity towards its signaling partners Ire1 alpha and PERK is differently modulated by an unfolded protein client

Autor(es)

Stan, Razvan C. ; Silva, Raissa L. ; de Camargo, Maristela M.

• Tipo de documento: Artigo Científico
• Fonte: Biochemical and Biophysical Research Communications; v. 487, n. 2, p. 375-380, MAY 27 2017.
• Citações Web of Science: 2

Resumo

Protein-folding stress is characteristic of specialized secretory cells and plays a dominant role in a multitude of diseases. The unfolded protein response (UPR) thus triggered is a proteostatic signaling network that adapts the protein-folding capacity of the endoplasmic reticulum to the cellular demands. We have measured the binding affinities between human GRP78, an essential chaperone located in ER, and two transmembrane UPR sensors (human PERK and Irela), with or without the addition of an unfolded protein client. We reveal distinct binding affinities between the binary and ternary complexes thus formed, that suggest a preference for the PERK signaling branch under stress, and a predilection for the GRP78-UPR sensor complex formation upon stressor removal. These results imply a gated UPR mechanism that tunes the overall cellular behavior to the accumulation of unfolded proteins. (C) 2017 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 11/51778-6 - Estudo funcional da via Unfolded Protein Response em linfócitos B humanos: hipogamaglobulinemia primária como modelo de disfunção da UPR
• Beneficiário: Maristela Martins de Camargo
• Modalidade de apoio: Auxílio à Pesquisa - Regular