GRP94: An HSP90-like protein specialized for protein folding and quality control in the endoplasmic reticulum

TY - JOUR

T1 - GRP94

T2 - An HSP90-like protein specialized for protein folding and quality control in the endoplasmic reticulum

AU - Marzec, Michal

AU - Eletto, Davide

AU - Argon, Yair

N1 - Copyright © 2011 Elsevier B.V. All rights reserved.

PY - 2012/3

Y1 - 2012/3

N2 - Glucose-regulated protein 94 is the HSP90-like protein in the lumen of the endoplasmic reticulum and therefore it chaperones secreted and membrane proteins. It has essential functions in development and physiology of multicellular organisms, at least in part because of this unique clientele. GRP94 shares many biochemical features with other HSP90 proteins, in particular its domain structure and ATPase activity, but also displays distinct activities, such as calcium binding, necessitated by the conditions in the endoplasmic reticulum. GRP94's mode of action varies from the general HSP90 theme in the conformational changes induced by nucleotide binding, and in its interactions with co-chaperones, which are very different from known cytosolic co-chaperones. GRP94 is more selective than many of the ER chaperones and the basis for this selectivity remains obscure. Recent development of molecular tools and functional assays has expanded the spectrum of clients that rely on GRP94 activity, but it is still not clear how the chaperone binds them, or what aspect of folding it impacts. These mechanistic questions and the regulation of GRP94 activity by other proteins and by post-translational modification differences pose new questions and present future research avenues. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90).

AB - Glucose-regulated protein 94 is the HSP90-like protein in the lumen of the endoplasmic reticulum and therefore it chaperones secreted and membrane proteins. It has essential functions in development and physiology of multicellular organisms, at least in part because of this unique clientele. GRP94 shares many biochemical features with other HSP90 proteins, in particular its domain structure and ATPase activity, but also displays distinct activities, such as calcium binding, necessitated by the conditions in the endoplasmic reticulum. GRP94's mode of action varies from the general HSP90 theme in the conformational changes induced by nucleotide binding, and in its interactions with co-chaperones, which are very different from known cytosolic co-chaperones. GRP94 is more selective than many of the ER chaperones and the basis for this selectivity remains obscure. Recent development of molecular tools and functional assays has expanded the spectrum of clients that rely on GRP94 activity, but it is still not clear how the chaperone binds them, or what aspect of folding it impacts. These mechanistic questions and the regulation of GRP94 activity by other proteins and by post-translational modification differences pose new questions and present future research avenues. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90).

KW - Amino Acid Sequence

KW - Animals

KW - Endoplasmic Reticulum

KW - HSP70 Heat-Shock Proteins

KW - HSP90 Heat-Shock Proteins

KW - Humans

KW - Membrane Proteins

KW - Molecular Sequence Data

KW - Protein Folding

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Review

U2 - 10.1016/j.bbamcr.2011.10.013

DO - 10.1016/j.bbamcr.2011.10.013

M3 - Review

C2 - 22079671

SN - 0006-3002

VL - 1823

SP - 774

EP - 787

JO - B B A - Reviews on Cancer

JF - B B A - Reviews on Cancer

IS - 3

ER -