Protein shapeshifter

The crystal structure of the chaperonin complex from the bacterium Thermus thermophilus is revealing new clues about how this giant protein complex does its job of folding new or damaged proteins within cells.

The problem of protein folding is one of the biggest challenges facing biomedical science today and is at the root of many disorders including the prion diseases and Alzheimer's disease. So Iwata of Imperial College London and colleagues there and at Tokyo Institute of Technology, the Japan Science and Technology Agency, and Osaka University, solved the structure of the chaperonin complex and announce their findings in the August issue of Structure.

Solving the structure of the chaperonin complex will provide valuable new insights into how proteins are folded into their active shape and how medical intervention might one day assist in the re-folding of damaged proteins when things go wrong. Iwata and his colleagues have found that the complex consists of three separate parts - two identical "cage" units lashed back to back, and a "cap" unit that sits on top of the cage, acting as a molecular stopper. Each unit of the cage or cap is made up of seven separate polypeptide chains. An unfolded or denatured protein can fit inside the cage allowing the chaperonin to refold it, a process that takes a mere ten seconds. "It's huge," explains Iwata, "The cavity can accommodate even very large proteins. It makes the perfect environment for the protein to fold."

Paul Sigler at Yale University reported a 2.8 angstrom resolution structure of the chaperonin complex from the gut bacterium Escherichia coli. Iwata explains that T. thermophilus provides a closer analogue to the chaperonin found in human cells and reveals the irregular oval interior of the cage. T. thermophilus is a highly thermophilic bacteria, first discovered in hot deep-sea vents, but despite its bizarre habitat its proteins resemble those found in plant and animal mitochondria far more than do those of gut bacteria.

The Imperial researchers hope to capture chaperonin in the act of refolding a denatured protein. They already have clues about the type of proteins it can refold and so will attempt to crystallise a chaperonin-protein complex. "We'd like to be the first to really know what happens, when the protein is enclosed and caught in the act," says Iwata.

Structure of Chaperonin protein.


Likely clues about the chaperoning proteins could emerge from the sea (Credit: David Bradley)