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.
N1 - Funding Information:
Funding for this project was provided by the Howard Hughes Medical Institute and University of California discovery grant bio03-10401 (to D.A.A.) as well as National Institutes of Health grant PN2 EY016525 (to A.S.). K.A.K. was supported by a NSDEG graduate fellowship. F.F. is grateful for a long-term fellowship from the Human Frontier Science Project Organization. We wish to thank the staff at the Advanced Light Source SIBYLS beamline 12.3.1 (especially G. Hura), the Stanford Synchrotron Radiation Laboratory beamline 4-2 (especially H. Tsuruta), and the Advanced Photon Source Biocat beamline 18-ID. A special thanks to C. Cunningham, D. Southworth, U. Boettcher, T. Street, and L. Lavery for many helpful discussions and comments on the manuscript.
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
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U2 - 10.1016/j.str.2008.01.021
DO - 10.1016/j.str.2008.01.021
M3 - Article
C2 - 18462680
AN - SCOPUS:42949147146
SN - 0969-2126
VL - 16
SP - 755
EP - 765
JO - Structure
JF - Structure
IS - 5
ER -