The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The unfolded or partially folded polypeptides, which are often intermediates in the folding pathway, are stabilized by chaperones, leading to the final correctly folded state. Without chaperones, the unfolded or partially folded polypeptides may misfold or form insoluble aggregates. This is particularly observed in proteins in which the carboxy or C-terminus is required for the correct folding of the amino or N-terminus. In such cases, a chaperone can bind and stabilize the N-terminal part of the polypeptide in an unfolded conformation until the rest of the peptide chain is synthesized and the whole protein can fold correctly.
Chaperones can also stabilize unfolded polypeptide chains as they are transported into subcellular organelles. For instance, during the transfer of proteins into the mitochondria from the cytosol, it is easier for partially unfolded conformations to be transported across the mitochondrial membrane. During the transport, the partially unfolded polypeptides are stabilized by chaperones.
Additionally, chaperones play an important role in the assembly of proteins that have a complex structure, such as multi-subunit proteins. These proteins comprise multiple polypeptide chains – each of which needs to be correctly folded and then assembled in a specific manner. In the processes involved, chaperones assist in protein folding and the stabilization of unassociated components while other parts of the protein are undergoing assembly.
