Amino acid substitutions influencing intracellular protein folding pathways

Abstract

Though an increasing variety of chaperonins are emerging as important factors in directing polypeptide chain folding off the ribosome, the primary amino acid sequence remains the major determinant of final conformation. The ability to identify cytoplasmic folding intermediates in the formation of the tailspike endorhamnosidase of phage P22 has made it possible to isolate two classes of mutations influencing folding intermediates — temperature-sensitive folding mutations and global suppressors of tsf mutants. These and related amino acid substitutions in eukaryotic proteins are discussed in the context of inclusion body formation and problems in the recovery of correctly folded proteins.