Fig. 1: Overview of key steps in client transfer.
From: Mechanism of client loading from BiP to Grp94 and its disruption by select inhibitors
In the ATP conformation, the BiP SBD (gray) and BiP NBD (navy blue) are docked and the SBD lid (gray rectangle) is open. Upon ATP hydrolysis, SBD lid closure can trap a client protein (black squiggle). In delivery, BiP binds Grp94 in the open conformation via interface I11 (light green). Grp94 NTD is in orange, Grp94 MD is in dark green, and Grp94 CTD is in light blue. The inset highlights a conserved salt bridge at interface I (Hsp70E218:Hsp90K419 from PDB: 7KW7). For client loading, there are two candidate structural models for the Grp94 C’ state, based on the coiled-coil structure21 (PDB: 5F3K) and the semi-closed structure10 (PDB: 7KW7) of Hsp90. In the semi-closed structure, interface II (pink) is formed. The lower inset highlights key residues at interface II in the semi-closed structure of Hsp70/Hsp90 (PDB: 7KW7). The upper inset highlights the crossing of N-terminal α-helices in the coiled-coil structure. In the last step, Grp94 traps the client protein upon ATP-dependent closure.
