Conformational constraints in protein degradation by the 20S proteasome

Abstract

Conformationally stabilized peptides and unfolding intermediates of bovine α-lactalbumin have been used to define the degree of unfolding required for degradation by 20S proteasomes. It appears that complete unfolding and the absence of disulphide bonds are prerequisites for degradation, suggesting that a relatively narrow opening controls access to the inner proteolytic compartment of the barrel-shaped proteasome. This is corroborated by electron microscopy studies showing that the insulin B-chain, which is otherwise easily degraded, cannot pass the orifice of this putative peptide channel when a Nanogold^™ particle with a diameter of ∼ 2 nm is covalently attached to it.