Heat-induced oligomerization of the molecular chaperone Hsp90: Inhibition by ATP and geldanamycin and activation by transition metal oxyanions

Ahmed Chadli, Moncef M. Ladjimi, Etienne Emile Baulieu, Maria Grazia Catelli

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

It has been previously reported that heat shock protein 90 (Hsp90) oligomerizes at high temperatures and displays concomitantly a novel chaperone activity (Yonehara, M., Minami, Y., Kawata, Y., Nagai, J., and Yahara, I. (1996) J. Biol. Chem., 271, 2641-2645). In order to better define these oligomerization properties at high temperatures and to know whether they are influenced by modulators of Hsp90 function, heat-induced oligomerization of highly purified dimeric Hsp90 has been investigated over a wide range of temperature and protein concentrations by native polyacrylamide gel electrophoresis and size exclusion chromatography. Whereas below 50 °C, the dimeric form is maintained over a large range of concentrations, at the critical temperature of 50 °C, a sharp transition from dimeric to higher order oligomeric species takes place within minutes, in a highly ordered process, suggesting that a conformational change, leading to the appearance of a new oligomerization site, occurs in Hsp90 dimer. Moreover, at and above the critical temperature, the extent of oligomerization increases with Hsp90 concentration. Formation of high order oligomers at high temperatures is sensitive to modulators of Hsp90 function. ATP and geldanamycin, both known to bind to the same pocket of Hsp90, are inhibitors of this process, whereas molybdate, vanadate, and Nonidet P-40, which are thought to increase surface hydrophobicity of the protein, are activators. Thus, oligomerization of Hsp90 at high temperatures may be mediated through hydrophobic interactions that are hindered by ligands and favored by transition metal oxyanions. The fact that the heat-induced oligomerization of Hsp90 is affected by specific ligands that modulate its properties also suggests that this process may be involved in cell protection during heat shock.

Original languageEnglish (US)
Pages (from-to)4133-4139
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number7
DOIs
StatePublished - Feb 12 1999
Externally publishedYes

Fingerprint

HSP90 Heat-Shock Proteins
Oligomerization
Molecular Chaperones
Transition metals
Hot Temperature
Adenosine Triphosphate
Metals
Chemical activation
Temperature
Hydrophobic and Hydrophilic Interactions
Modulators
Ligands
Native Polyacrylamide Gel Electrophoresis
geldanamycin
Vanadates
Cytoprotection
Size exclusion chromatography
Hydrophobicity
Electrophoresis
Oligomers

ASJC Scopus subject areas

  • Biochemistry

Cite this

Heat-induced oligomerization of the molecular chaperone Hsp90 : Inhibition by ATP and geldanamycin and activation by transition metal oxyanions. / Chadli, Ahmed; Ladjimi, Moncef M.; Baulieu, Etienne Emile; Catelli, Maria Grazia.

In: Journal of Biological Chemistry, Vol. 274, No. 7, 12.02.1999, p. 4133-4139.

Research output: Contribution to journalArticle

@article{3a225b1b2eba42ee9c2e1f997087fadb,
title = "Heat-induced oligomerization of the molecular chaperone Hsp90: Inhibition by ATP and geldanamycin and activation by transition metal oxyanions",
abstract = "It has been previously reported that heat shock protein 90 (Hsp90) oligomerizes at high temperatures and displays concomitantly a novel chaperone activity (Yonehara, M., Minami, Y., Kawata, Y., Nagai, J., and Yahara, I. (1996) J. Biol. Chem., 271, 2641-2645). In order to better define these oligomerization properties at high temperatures and to know whether they are influenced by modulators of Hsp90 function, heat-induced oligomerization of highly purified dimeric Hsp90 has been investigated over a wide range of temperature and protein concentrations by native polyacrylamide gel electrophoresis and size exclusion chromatography. Whereas below 50 °C, the dimeric form is maintained over a large range of concentrations, at the critical temperature of 50 °C, a sharp transition from dimeric to higher order oligomeric species takes place within minutes, in a highly ordered process, suggesting that a conformational change, leading to the appearance of a new oligomerization site, occurs in Hsp90 dimer. Moreover, at and above the critical temperature, the extent of oligomerization increases with Hsp90 concentration. Formation of high order oligomers at high temperatures is sensitive to modulators of Hsp90 function. ATP and geldanamycin, both known to bind to the same pocket of Hsp90, are inhibitors of this process, whereas molybdate, vanadate, and Nonidet P-40, which are thought to increase surface hydrophobicity of the protein, are activators. Thus, oligomerization of Hsp90 at high temperatures may be mediated through hydrophobic interactions that are hindered by ligands and favored by transition metal oxyanions. The fact that the heat-induced oligomerization of Hsp90 is affected by specific ligands that modulate its properties also suggests that this process may be involved in cell protection during heat shock.",
author = "Ahmed Chadli and Ladjimi, {Moncef M.} and Baulieu, {Etienne Emile} and Catelli, {Maria Grazia}",
year = "1999",
month = "2",
day = "12",
doi = "10.1074/jbc.274.7.4133",
language = "English (US)",
volume = "274",
pages = "4133--4139",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "7",

}

TY - JOUR

T1 - Heat-induced oligomerization of the molecular chaperone Hsp90

T2 - Inhibition by ATP and geldanamycin and activation by transition metal oxyanions

AU - Chadli, Ahmed

AU - Ladjimi, Moncef M.

AU - Baulieu, Etienne Emile

AU - Catelli, Maria Grazia

PY - 1999/2/12

Y1 - 1999/2/12

N2 - It has been previously reported that heat shock protein 90 (Hsp90) oligomerizes at high temperatures and displays concomitantly a novel chaperone activity (Yonehara, M., Minami, Y., Kawata, Y., Nagai, J., and Yahara, I. (1996) J. Biol. Chem., 271, 2641-2645). In order to better define these oligomerization properties at high temperatures and to know whether they are influenced by modulators of Hsp90 function, heat-induced oligomerization of highly purified dimeric Hsp90 has been investigated over a wide range of temperature and protein concentrations by native polyacrylamide gel electrophoresis and size exclusion chromatography. Whereas below 50 °C, the dimeric form is maintained over a large range of concentrations, at the critical temperature of 50 °C, a sharp transition from dimeric to higher order oligomeric species takes place within minutes, in a highly ordered process, suggesting that a conformational change, leading to the appearance of a new oligomerization site, occurs in Hsp90 dimer. Moreover, at and above the critical temperature, the extent of oligomerization increases with Hsp90 concentration. Formation of high order oligomers at high temperatures is sensitive to modulators of Hsp90 function. ATP and geldanamycin, both known to bind to the same pocket of Hsp90, are inhibitors of this process, whereas molybdate, vanadate, and Nonidet P-40, which are thought to increase surface hydrophobicity of the protein, are activators. Thus, oligomerization of Hsp90 at high temperatures may be mediated through hydrophobic interactions that are hindered by ligands and favored by transition metal oxyanions. The fact that the heat-induced oligomerization of Hsp90 is affected by specific ligands that modulate its properties also suggests that this process may be involved in cell protection during heat shock.

AB - It has been previously reported that heat shock protein 90 (Hsp90) oligomerizes at high temperatures and displays concomitantly a novel chaperone activity (Yonehara, M., Minami, Y., Kawata, Y., Nagai, J., and Yahara, I. (1996) J. Biol. Chem., 271, 2641-2645). In order to better define these oligomerization properties at high temperatures and to know whether they are influenced by modulators of Hsp90 function, heat-induced oligomerization of highly purified dimeric Hsp90 has been investigated over a wide range of temperature and protein concentrations by native polyacrylamide gel electrophoresis and size exclusion chromatography. Whereas below 50 °C, the dimeric form is maintained over a large range of concentrations, at the critical temperature of 50 °C, a sharp transition from dimeric to higher order oligomeric species takes place within minutes, in a highly ordered process, suggesting that a conformational change, leading to the appearance of a new oligomerization site, occurs in Hsp90 dimer. Moreover, at and above the critical temperature, the extent of oligomerization increases with Hsp90 concentration. Formation of high order oligomers at high temperatures is sensitive to modulators of Hsp90 function. ATP and geldanamycin, both known to bind to the same pocket of Hsp90, are inhibitors of this process, whereas molybdate, vanadate, and Nonidet P-40, which are thought to increase surface hydrophobicity of the protein, are activators. Thus, oligomerization of Hsp90 at high temperatures may be mediated through hydrophobic interactions that are hindered by ligands and favored by transition metal oxyanions. The fact that the heat-induced oligomerization of Hsp90 is affected by specific ligands that modulate its properties also suggests that this process may be involved in cell protection during heat shock.

UR - http://www.scopus.com/inward/record.url?scp=0033548270&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033548270&partnerID=8YFLogxK

U2 - 10.1074/jbc.274.7.4133

DO - 10.1074/jbc.274.7.4133

M3 - Article

C2 - 9933607

AN - SCOPUS:0033548270

VL - 274

SP - 4133

EP - 4139

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 7

ER -