(A and B) Pore-1 loop residues grip the substrate, as observed in this view looking down the axial channel. The substrate is modeled as poly-Ala. (A) In Conformation A, the X1 protomer is disengaged from the substrate in the US position (red arrow) and shows noticeable flexibility in its pore-1 loop. (B) In Conformation B, the X1 protomer contacts the substrate but the X6 protomer has disengaged into the LS position (red arrows). (C and D) Model of substrate and interacting residues, along with schematic, viewed perpendicular to the axial channel. (C) In Conformation A, only the Tyr153 residue of the pore-1 loop makes significant contacts with the substrate; the five protomers (X2, X3, X4, X5, X6) form a downward spiral surrounding the backbone of the substrate chain, extending to the apical surface of ClpP. (D) In Conformation B, in addition to the five Tyr153 residues from the five gripping protomers (X1, X2, X3, X4, X5), more contacts are formed: Ser197 and Ile198 from the pore-2 loop of the X1 protomer and His230 from the RKH loop of the X5 protomer. (E) Substrate-induced conformational changes of the X6 pore-1 loop upon releasing client. When the X6 protomer is substrate engaged its pore-1 loop forms a lasso like conformation, with Tyr153 and Val154 both pointing toward the axial channel (left). When disengaged, a part of the pore-1 loop becomes an α-helix, with Val154 and Tyr153 no longer pointing outwards (right). (F) Architecture of the additional contacts made by the pore-2 and RKH loops from the X1 and X5 protomers, respectively.