Chaperones and Catalyzed Protein Folding - Protein Synthesis

Chaperones and Catalyzed Protein Folding

In the 1960s Anfinson showed that pancreatic ribonuclease could be denatured and, when placed in buffers that resemble intracellular solvent conditions, would renature. This finding led to the belief that all proteins fold in vivo without the assistance of other proteins. Conse-quently it has come as a second surprise to find that virtually all types of cells, from bacteria to higher eukaryotes, possess proteins that appear to assist the folding of nascent proteins. Although the majority of the cell’s proteins do fold on their own, an important number utilize auxiliary folding proteins.

In the E. coli cytoplasm, some newly synthesized and therefore unfolded proteins first interact with DnaK and then DnaJ. Binding to these two proteins prevents premature misfolding or aggregation. Then, with the assistance of GrpE, and the hydrolysis of ATP, the oligomeric protein GroEL/ES binds. This complex recognizes secondary structure of polypeptides and appears to stabilize conformational intermediates as the newly synthesized proteins settle from what is called the molten globule state into their final compact folded state.

Eukaryotic cells possess analogs of DnaK and GroEL. These are known as the heat shock proteins Hsp70 and Hsp60. The synthesis of these 70,000 and 60,000 dalton proteins is dramatically increased by exposure of the cells to heat or other agents that denature proteins. Members of these families help maintain polypeptides in the extended state for import into mitochondria and then help fold the imported polypeptide. The proteins are called chaperones for their roles in assist-ing the transport process.