Figure 3. Models for Hsp70 protein translocation mechanism.

A) Trapping or biased diffusion: 1) an unfolded protein moving through a pore can diffuse in either direction, 2) binding of Hsp70 to the protein on the downstream side of the pore blocks its upstream, but not downstream, diffusion and 3) whenever diffusion exposes another protein segment with an Hsp70-binding site on the downstream side of the pore another Hsp70 can bind. Eventually, the entire protein will be transported to the downstream side of the pore. B) Directed pulling: 2) the protein is bound by Hsp70, and the latter physically abuts or binds to the transport pore and 3) using the pore as a fulcrum, Hsp70 undergoes a conformational changes that pulls the protein in the downstream direction. C) Entropic pulling: 1) the unfolded protein segment that has emerged on the downstream side of the pore can wiggle around in a volume limited only by the wall presented by the pore and membrane, 2) binding of Hsp70 near the pore restricts the freedom of movement of the unfolded protein segment and the Hsp70, decreasing the entropy (ΔS) and3) emergence of more protein on the downstream side of the pore increases the freedom of movement of the unfolded protein and the associated Hsp70, increasing the entropy.