Questionary Akis "Chaperones"

Trigger Factor has an N-terminal ribosome-binding domain, a PPIase domain, and a C-terminal substrate-binding domain; the protein has a characteristic seahorse-like structure

• N-terminal ATPase/nucleotide-binding domain

• substrate-binding domain,

• C-terminal lid/co-chaperone interaction region

• ATPase domain binds and hydrolyzes ATP

• the substrate-binding domain recognizes unfolded peptide segments,

• lid/C-terminal region regulates substrate capture and release.

• ATP-bound Hsp70 is in an open, low-affinity state for substrate binding

• ATP hydrolysis converts it to the ADP-bound,

• closed, high-affinity state; nucleotide exchange then releases ADP, ATP rebinds, and the substrate is released

DnaJ/Hsp40 recruits Hsp70 to substrates and stimulates the ATPase activity of Hsp70 via its J-domain.

• N-terminal

• ATP-binding domain

• middle domain,

• C-terminal dimerization domain

• N-terminal domain binds ATP

• the middle domain contributes to client binding and ATP hydrolysis

• C-terminal domain mediates dimerization and binds TPR-containing co-chaperones.

• Hsp90 starts as an open dimer; ATP binding induces conformational change and N-terminal dimerization/closure; co-chaperones regulate this cycle; ATP hydrolysis returns Hsp90 to the open state and allows client release or transfer.

• The lecture highlights Hop, Cdc37, Aha1, and p23

• Hop and Cdc37 delay ATP hydrolysis

• Aha1 accelerates ATP hydrolysis by stabilizing NTD dimerization

• p23 stabilizes the closed dimer and slows substrate release

• kinases

• steroid/glucocorticoid receptors

• transcription factors such as HSF and HIF,

• cytoskeletal proteins like actin and tubulin.

• An unfolded substrate binds GroEL,

• ATP binds the ring

• GroES caps the chamber, the protein folds in the enclosed cavity

• after ATP hydrolysis and cap release the substrate is released and the system resets.

• GroEL is a double-ring chaperonin with two heptameric rings

• and GroES is the heptameric cap that closes one ring to form the folding chamber.

important for regulating disaggregase activity and transmitting conformational changes required for aggregate dissolution.