Thermolabile folding intermediates: inclusion body precursors and chaperonin substrates.

摘要: An unexpected aspect of the expression cloned genes is frequent failure newly synthesized polypeptide chains to reach their native state, accumulating instead as insoluble inclusion bodies. Amyloid deposits represent a related state associated with variety human diseases. The critical folding intermediates at juncture productive and off-pathway aggregation reaction have been identified for phage P22 tailspike coat proteins. Though parallel beta coil thermostable, an early intracellular intermediate thermolabile. As temperature increased, this species partitions bodies, kinetic trap within cell. earliest along in vitro pathway, sequential multimers thermolabile intermediates, directly by gel electrophoresis. Temperature-sensitive (tsf) mutations identify sites domain, which direct junctional down pathway. Global suppressors tsf mutants inhibit pathway rescuing mutant chains. These important avoiding aggregation. Coat also partition bodies increased. are suppressed overexpression GroE chaperonin, indicating that physiological substrate GroE. We suggest many proteins likely pathways, will be precursors body formation elevated temperatures therefore substrates heat shock chaperonins.