The door to the ER is closed by BiP-ADP and opened with BiP-ATP.

Agate that guards the translocon is opened and closed by ATP cycles that also give the same protein chaperone activity, as shown on page 389 by Alder et al.

The translocon is an aqueous pore in the ER membrane through which secreted proteins pass during translation. To prevent the unwanted passage of ions, unused pores are plugged on the lumen side by the action of BiP. Within the ER, BiP is also an Hsp70-like chaperone. Alder et al. now find that the ATP-dependent changes in substrate affinity that make BiP an efficient chaperone also give it its translocon gating ability.

ADP-bound Hsp70 chaperones bind tightly to their substrates, whereas ATP induces a conformational change that opens the substrate-binding pocket. Cycles of binding and release allow BiP to help its substrates fold properly.

For its gating activity, BiP's “substrate” appears to be an as-yet-unidentified translocon component. Only ADP-bound BiP was able to seal the translocon pore. Pore opening, conversely, required ATP-induced conformational changes, presumably to release the translocon protein from BiP's substrate-binding pocket.

Interactions with a protein containing a J-domain are also required for both its chaperone and gating activities. Perhaps the translocon-associated J-domain protein binds to a regulator that suppresses nucleotide exchange on BiP, thus keeping the door shut until the translocating protein needs to enter.