Free energy landscape of substrate passing inside proteasome - activator complex

Ishida, Hisashi

Proteasome is involved in the degradation of the majority of cellular proteins. Proteasome activators bind to 20S proteasome core particle (CP) and facilitate opening a gate on the end of the CP. Then, the CP allows protein substrates to move into its interior through a channel between the gate and the alpha-annulus in order to hydrolyze the substrates to small fragments, and releases the products outside. To understand the gating mechanism of the CP, molecular dynamics simulations of the CP complexed with a PAN (analog of ATP-dependent 19S activator)-like activator, and of the CP complexed with an ATP-independent PA26 activator. The free-energies of the translocation of a poly-peptide substrate through the channel of these complexes were estimated.