Multiple Conformations of E. coli Hsp90 in Solution

Insights into the Conformational Dynamics of Hsp90

Kristin A. Krukenberg, Friedrich Förster, Luke M. Rice, Andrej Sali, David A. Agard

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

Hsp90, an essential eukaryotic chaperone, depends upon its intrinsic ATPase activity for function. Crystal structures of the bacterial Hsp90 homolog, HtpG, and the yeast Hsp90 reveal large domain rearrangements between the nucleotide-free and the nucleotide-bound forms. We used small-angle X-ray scattering and recently developed molecular modeling methods to characterize the solution structure of HtpG and demonstrate how it differs from known Hsp90 conformations. In addition to this HtpG conformation, we demonstrate that under physiologically relevant conditions, multiple conformations coexist in equilibrium. In solution, nucleotide-free HtpG adopts a more extended conformation than observed in the crystal, and upon the addition of AMPPNP, HtpG is in equilibrium between this open state and a closed state that is in good agreement with the yeast AMPPNP crystal structure. These studies provide a unique view of Hsp90 conformational dynamics and provide a model for the role of nucleotide in effecting conformational change.

Original languageEnglish (US)
Pages (from-to)755-765
Number of pages11
JournalStructure
Volume16
Issue number5
DOIs
StatePublished - May 7 2008

Fingerprint

Nucleotides
Adenylyl Imidodiphosphate
Escherichia coli
Yeasts
Bacterial Structures
Adenosine Triphosphatases
X-Rays

Keywords

  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Multiple Conformations of E. coli Hsp90 in Solution : Insights into the Conformational Dynamics of Hsp90. / Krukenberg, Kristin A.; Förster, Friedrich; Rice, Luke M.; Sali, Andrej; Agard, David A.

In: Structure, Vol. 16, No. 5, 07.05.2008, p. 755-765.

Research output: Contribution to journalArticle

Krukenberg, Kristin A. ; Förster, Friedrich ; Rice, Luke M. ; Sali, Andrej ; Agard, David A. / Multiple Conformations of E. coli Hsp90 in Solution : Insights into the Conformational Dynamics of Hsp90. In: Structure. 2008 ; Vol. 16, No. 5. pp. 755-765.
@article{0e80c471a74947199e2fca245a3b340b,
title = "Multiple Conformations of E. coli Hsp90 in Solution: Insights into the Conformational Dynamics of Hsp90",
abstract = "Hsp90, an essential eukaryotic chaperone, depends upon its intrinsic ATPase activity for function. Crystal structures of the bacterial Hsp90 homolog, HtpG, and the yeast Hsp90 reveal large domain rearrangements between the nucleotide-free and the nucleotide-bound forms. We used small-angle X-ray scattering and recently developed molecular modeling methods to characterize the solution structure of HtpG and demonstrate how it differs from known Hsp90 conformations. In addition to this HtpG conformation, we demonstrate that under physiologically relevant conditions, multiple conformations coexist in equilibrium. In solution, nucleotide-free HtpG adopts a more extended conformation than observed in the crystal, and upon the addition of AMPPNP, HtpG is in equilibrium between this open state and a closed state that is in good agreement with the yeast AMPPNP crystal structure. These studies provide a unique view of Hsp90 conformational dynamics and provide a model for the role of nucleotide in effecting conformational change.",
keywords = "PROTEINS",
author = "Krukenberg, {Kristin A.} and Friedrich F{\"o}rster and Rice, {Luke M.} and Andrej Sali and Agard, {David A.}",
year = "2008",
month = "5",
day = "7",
doi = "10.1016/j.str.2008.01.021",
language = "English (US)",
volume = "16",
pages = "755--765",
journal = "Structure with Folding & design",
issn = "0969-2126",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Multiple Conformations of E. coli Hsp90 in Solution

T2 - Insights into the Conformational Dynamics of Hsp90

AU - Krukenberg, Kristin A.

AU - Förster, Friedrich

AU - Rice, Luke M.

AU - Sali, Andrej

AU - Agard, David A.

PY - 2008/5/7

Y1 - 2008/5/7

N2 - Hsp90, an essential eukaryotic chaperone, depends upon its intrinsic ATPase activity for function. Crystal structures of the bacterial Hsp90 homolog, HtpG, and the yeast Hsp90 reveal large domain rearrangements between the nucleotide-free and the nucleotide-bound forms. We used small-angle X-ray scattering and recently developed molecular modeling methods to characterize the solution structure of HtpG and demonstrate how it differs from known Hsp90 conformations. In addition to this HtpG conformation, we demonstrate that under physiologically relevant conditions, multiple conformations coexist in equilibrium. In solution, nucleotide-free HtpG adopts a more extended conformation than observed in the crystal, and upon the addition of AMPPNP, HtpG is in equilibrium between this open state and a closed state that is in good agreement with the yeast AMPPNP crystal structure. These studies provide a unique view of Hsp90 conformational dynamics and provide a model for the role of nucleotide in effecting conformational change.

AB - Hsp90, an essential eukaryotic chaperone, depends upon its intrinsic ATPase activity for function. Crystal structures of the bacterial Hsp90 homolog, HtpG, and the yeast Hsp90 reveal large domain rearrangements between the nucleotide-free and the nucleotide-bound forms. We used small-angle X-ray scattering and recently developed molecular modeling methods to characterize the solution structure of HtpG and demonstrate how it differs from known Hsp90 conformations. In addition to this HtpG conformation, we demonstrate that under physiologically relevant conditions, multiple conformations coexist in equilibrium. In solution, nucleotide-free HtpG adopts a more extended conformation than observed in the crystal, and upon the addition of AMPPNP, HtpG is in equilibrium between this open state and a closed state that is in good agreement with the yeast AMPPNP crystal structure. These studies provide a unique view of Hsp90 conformational dynamics and provide a model for the role of nucleotide in effecting conformational change.

KW - PROTEINS

UR - http://www.scopus.com/inward/record.url?scp=42949147146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42949147146&partnerID=8YFLogxK

U2 - 10.1016/j.str.2008.01.021

DO - 10.1016/j.str.2008.01.021

M3 - Article

VL - 16

SP - 755

EP - 765

JO - Structure with Folding & design

JF - Structure with Folding & design

SN - 0969-2126

IS - 5

ER -