Chaperones and Folding Catalysts Involved in the General Protein Secretion Pathway of Escherichia Coli

Abstract

Cytoplasmic proteins leaving the exit site of the ribosome fold into their native conformation, whereas most proteins destined for the inner membrane or the extracytoplasmic environment are targeted to the inner membrane (IM). These latter proteins are protected against premature folding, misfolding, aggregation and degradation. These proteins are inserted into or translocated across the inner membrane in a non-native state. Folding and assembly into their native conformation occurs in or at the membrane but outside the cytoplasm. Proteins that are translocated across the IM either remain in the periplasm or are incorporated into the outer membrane. In addition, they can be translocated across the outer membrane where they can end up at the outer cell surface or in the extracellular environment. The precision and speed of these processes is ensured by targeting factors, molecular chaperones and folding catalysts. Molecular chaperones are molecules that prevent unfavorable interactions of a substrate and guides the substrate (a protein) into a productive export and folding pathway. In contrast, folding catalysts speed up the kinetics of folding by catalysing intrinsic rate limiting steps in protein folding, like the cis/trans isomerization of X-Pro peptide bonds and disulfide bond formation.