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Identification of novel quaternary domain interactions in the Hsp90 chaperone, GRP94.

Publication ,  Journal Article
Chu, F; Maynard, JC; Chiosis, G; Nicchitta, CV; Burlingame, AL
Published in: Protein Sci
June 2006

The structural basis for the coupling of ATP binding and hydrolysis to chaperone activity remains a central question in Hsp90 biology. By analogy to MutL, ATP binding to Hsp90 is thought to promote intramolecular N-terminal dimerization, yielding a molecular clamp functioning in substrate protein activation. Though observed in studies with recombinant domains, whether such quaternary states are present in native Hsp90s is unknown. In this study, native subunit interactions in GRP94, the endoplasmic reticulum Hsp90, were analyzed using chemical cross-linking in conjunction with tandem mass spectrometry. We report the identification of two distinct intermolecular interaction sites. Consistent with previous studies, one site comprises the C-terminal dimerization domain. The remaining site represents a novel intermolecular contact between the N-terminal and middle (M) domains of opposing subunits. This N+M domain interaction was present in the nucleotide-empty, ADP-, ATP-, or geldanamycin-bound states and could be selectively disrupted upon addition of synthetic geldanamycin dimers. These results identify a compact, intertwined quaternary conformation of native GRP94 and suggest that intersubunit N+M interactions are integral to the structural biology of Hsp90.

Duke Scholars

Published In

Protein Sci

DOI

ISSN

0961-8368

Publication Date

June 2006

Volume

15

Issue

6

Start / End Page

1260 / 1269

Location

United States

Related Subject Headings

  • Swine
  • Succinimides
  • Quinones
  • Protein Structure, Tertiary
  • Protein Structure, Quaternary
  • Protein Conformation
  • Molecular Chaperones
  • Models, Molecular
  • Membrane Proteins
  • Mass Spectrometry
 

Citation

APA
Chicago
ICMJE
MLA
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Chu, F., Maynard, J. C., Chiosis, G., Nicchitta, C. V., & Burlingame, A. L. (2006). Identification of novel quaternary domain interactions in the Hsp90 chaperone, GRP94. Protein Sci, 15(6), 1260–1269. https://doi.org/10.1110/ps.052065106
Chu, Feixia, Jason C. Maynard, Gabriela Chiosis, Christopher V. Nicchitta, and Alma L. Burlingame. “Identification of novel quaternary domain interactions in the Hsp90 chaperone, GRP94.Protein Sci 15, no. 6 (June 2006): 1260–69. https://doi.org/10.1110/ps.052065106.
Chu F, Maynard JC, Chiosis G, Nicchitta CV, Burlingame AL. Identification of novel quaternary domain interactions in the Hsp90 chaperone, GRP94. Protein Sci. 2006 Jun;15(6):1260–9.
Chu, Feixia, et al. “Identification of novel quaternary domain interactions in the Hsp90 chaperone, GRP94.Protein Sci, vol. 15, no. 6, June 2006, pp. 1260–69. Pubmed, doi:10.1110/ps.052065106.
Chu F, Maynard JC, Chiosis G, Nicchitta CV, Burlingame AL. Identification of novel quaternary domain interactions in the Hsp90 chaperone, GRP94. Protein Sci. 2006 Jun;15(6):1260–1269.

Published In

Protein Sci

DOI

ISSN

0961-8368

Publication Date

June 2006

Volume

15

Issue

6

Start / End Page

1260 / 1269

Location

United States

Related Subject Headings

  • Swine
  • Succinimides
  • Quinones
  • Protein Structure, Tertiary
  • Protein Structure, Quaternary
  • Protein Conformation
  • Molecular Chaperones
  • Models, Molecular
  • Membrane Proteins
  • Mass Spectrometry