Fig 5. Predictive model of a role for Hsp70 in cercarial honing.

(A) In the absence of strong host signals, Hsp70 binds tightly to its client protein, HHF, inhibiting its activity. (B) Host signals are transmitted through a cercarial signal transduction pathway, releasing Hsp70 inhibition of HHF, which functions in cercarial honing. (C) The inhibitor PES blocks Hsp70 activity by binding to the Hsp70 substrate binding domain and releasing Hsp70 inhibition of HHF, resulting in cercarial honing. (D) Addition of 10 mM ATP leads to release of HHF, possibly by binding to the Hsp70 ATPase domain and reducing its affinity for HHF, resulting in cercarial honing. (E) Addition of a non-hydrolyzable form of ATP leads to release of HHF, possibly by preventing ATP hydrolysis and maintaining the weak affinity state of Hsp70 for binding client proteins, resulting in cercarial honing.