| | why cant we say chaperone an enzyme?
tarun gupta wrote:
In short, the Hsc70-ATP complex has an open protein binding site, like a
spring-loaded mouse trap. It can reversibly bind to proteins, until
ATP-hydrolysis is stimulated by a co-chaperone, so the mouse trap snaps
shut. Phosphate is released and the resulting substrate-Hsc70-ADP
complex is very stable, until ADP/ATP-exchange is stimulated by a second
co-chaperone. This opens the protein binding site as well, so that the
protein can dissociate again. The whole mechanism is reminescent of that
of small G-proteins.
By localising the ATP-hydrolysis stimulating factor (DnaJ-like) at the
source structure and the ADP/ATP-exchange factor (GrpE-like) at the
destination, vectorial transport by Hsc70 is possible, based entirely on
Note that mitochondria contain an Hsc70-like protein, mtDnaK. Once the
nascent protein comes out of TIM, DnaK binds to it and thus prevents it
from slipping back through the TIM/TOM apparatus. So the release of the
protein from Hsc70 at the outside and binding by DnaK at the inside
create a "molecular ratchet" that ensures vectorial transport through
TOM/TIM (which is a gated pore, not a transporter).
Some researchers claim that in addition to this ratchet mechanism
conformational changes in DnaK after protein binding/ATP-hydrolysis and
changes of its interactions with the mt inner membrane actively pull the
substrate protein through the TOM/TIM channel. Final proof for this
hypothesis has not been obtained yet. Note however that Hsc70 can
cross-link glutamate decarboxylase (Gad65) to the membrane of secretory
vesicles in nerve cells, ensuring their efficient loading with GABA.
Thus such interactions of 70 kDa heat shock proteins with membrane and
protein are not unheared of.