• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Grp94, the endoplasmic reticulum Hsp90, has a similar solution conformation to cytosolic Hsp90 in the absence of nucleotide.

The molecular chaperone, Hsp90, is an essential eukaryotic protein that assists in the maturation and activation of client proteins. Hsp90 function depends upon the binding and hydrolysis of ATP, which causes large conformational rearrangements in the chaperone. Hsp90 is highly conserved from bacteria to eukaryotes, and similar nucleotide-dependent conformations have been demonstrated for the bacterial, yeast, and human proteins. There are, however, important species-specific differences in the ability of nucleotide to shift the conformation from one state to another. Although the role of nucleotide in conformation has been well studied for the cytosolic yeast and human proteins, the conformations found in the absence of nucleotide are less well understood. In contrast to cytosolic Hsp90, crystal structures of the endoplasmic reticulum homolog, Grp94, show the same conformation in the presence of both ADP and AMPPNP. This conformation differs from the yeast AMPPNP-bound crystal state, suggesting that Grp94 may have a different conformational cycle. In this study, we use small angle X-ray scattering and rigid body modeling to study the nucleotide free states of cytosolic yeast and human Hsp90s, as well as mouse Grp94. We show that all three proteins adopt an extended, chair-like conformation distinct from the extended conformation observed for the bacterial Hsp90. For Grp94, we also show that nucleotide causes a small shift toward the crystal state, although the extended state persists as the major population. These results provide the first evidence that Grp94 shares a conformational state with other Hsp90 homologs.

Pubmed ID: 19554567

Authors

  • Krukenberg KA
  • Böttcher UM
  • Southworth DR
  • Agard DA

Journal

Protein science : a publication of the Protein Society

Publication Data

September 17, 2009

Associated Grants

  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Apoproteins
  • Crystallography, X-Ray
  • Cytosol
  • Endoplasmic Reticulum
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • Humans
  • Membrane Proteins
  • Mice
  • Models, Molecular
  • Nucleotides
  • Protein Conformation
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Scattering, Small Angle