The GroEL/ES cycle diagrammed in Fig. 6-45 circulates only in the clockwise direction. Explain the basis for this irreversibility in terms of the sequence of structural and binding changes in the GroEL/ES system.

Figure 6-45

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ATP3 ADP ATP ATP Turn 180 www ADP ATP'S The trans ring with its bound ATP now becomes the cis ring. +7 (ADP) GroES The cis ring releases GroES cap, ADP, and a better-folded substrate protein. GroES N GroES cap binds to the GroEL ring. This induces a conformational change in the now cis ring, which releases the improperly folded protein into the enlarged cavity where it commences to refold. Better folded protein A second molecule of improperly folded substrate protein binds to the trans ring, followed by 7 ATP. my 72ATP ATP Improperly folded protein Within ~10 s the cis ring catalyzes the hydrolysis of its 7 bound ATPs and releases 2 the resulting P;, which weakens the interactions binding GroES to GroEL. GroEL/ES chaperonin ATP ADP ADP Substrate protein >cis ring -trans ring