Protein Folding and Misfolding

Unlike collagen, many biologically important proteins are not extended but globular.

This is usually important for their function, enzyme activity etc.

How does the protein get from its undefined shape following biosynthesis, to a unique folded state?

This is a big question, and one which is not very well understood.

If there is a single minimum but billions of intermediate states which could be accessed, how does the protein rapidly find the minimum?

Current thinking favours funnels in a rough energy landscape with funnels.

There may be several folding pathways, but it is clear that many states will not be accessed at all.

Trying to understand what the key intermediate states is is one of the main current challenges.

Point mutations are used to see which regions of the chain are important for determining the correct folding states.

Real protein folding may have more than one minimum, and different folding paths to the unique minimum are possible.

Misfolded Proteins

Nature has designed proteins to be pretty robust and they fold correctly most of the time.

But when things go wrong it can be catastropic – leading to diseases such as BSE/vCJD and Alzheimers.

These are known as amyloid diseases, as amyloid fibrils of misfolded protein are deposited in the body.

Transmission electron micrograph of a dilute suspension of the misfolded proteins shows the individual fibrils quite clearly.

Undiluted have quite different structures. In the SEM show aggregates of plates.

In the polarising microscope show spherulites.