Conformational plasticity of a BiP-GRP94 chaperone complex.

ABSTRACT: Hsp70 and Hsp90 chaperones and their regulatory cochaperones are critical for maintaining protein homeostasis. Glucose-regulated protein 94 (GRP94), the sole Hsp90 chaperone in the secretory pathway of mammalian cells, is essential for the maturation of important secretory and transmembrane proteins. Without the requirement of cochaperones, the Hsp70 protein BiP controls regulatory conformational changes of GRP94, the structural basis of which has remained elusive. Here we biochemically and structurally characterize the formation of a BiP-GRP94 chaperone complex and its transition to a conformation expected to support the loading of substrate proteins from BiP onto GRP94. BiP initially binds to the open GRP94 dimer through an interaction interface that is conserved among Hsp70 and Hsp90 pa

SUBMITTER: Brenner JC 

PROVIDER: S-EPMC12527940 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature