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 -