5ULS

Structure of GRP94 in the active conformation

Summary for 5ULS

• Entry DOI: 10.2210/pdb5uls/pdb
• Descriptor: Endoplasmin, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (3 entities in total)
• Functional Keywords: chaperone, endoplasmic reticulum, heat-shock protein, hsp90
• Biological source: Canis lupus familiaris (Dog); More
• Total number of polymer chains: 2
• Total formula weight: 160024.94

Authors

Huck, J.D.,Que, N.L.S.,Gewirth, D.T. (deposition date: 2017-01-25, release date: 2017-09-27, Last modification date: 2023-10-04)

Primary citation

Huck, J.D.,Que, N.L.,Hong, F.,Li, Z.,Gewirth, D.T.
Structural and Functional Analysis of GRP94 in the Closed State Reveals an Essential Role for the Pre-N Domain and a Potential Client-Binding Site.
Cell Rep, 20:2800-2809, 2017

PubMed Abstract: Hsp90 chaperones undergo ATP-driven conformational changes during the maturation of client proteins, populating a closed state upon ATP binding in which the N-terminal domains of the homodimer form a second inter-protomer dimer interface. A structure of GRP94, the endoplasmic reticulum hsp90, in a closed conformation has not been described, and the determinants that regulate closure are not well understood. Here, we determined the 2.6-Å structure of AMPPNP-bound GRP94 in the closed dimer conformation. The structure includes the pre-N domain, a region preceding the N-terminal domain that is highly conserved in GRP94, but not in other hsp90s. We show that the GRP94 pre-N domain is essential for client maturation, and we identify the pre-N domain as an important regulator of ATPase rates and dimer closure. The structure also reveals a GRP94:polypeptide interaction that partially mimics a client-bound state. The results provide structural insight into the ATP-dependent client maturation process of GRP94.

PubMed: 28930677
DOI: 10.1016/j.celrep.2017.08.079

Experimental method

X-RAY DIFFRACTION (2.622 Å)