Converting proteins into crystals

Proteins need to be transformed into 3-D crystals before their atomic structures and their properties can be analyzed. And scientists in the U.K. have successfully used a porous medium, or 'nucleant,' a material that encourages protein molecules to crystallize.

As you might know, proteins need to be transformed into 3-D crystals before their atomic structures and their properties can be analyzed. And production of high quality crystals from proteins has been a difficult task until now. But scientists in the U.K. have successfully used a porous medium, or 'nucleant,' a material that encourages protein molecules to crystallize. Their first step towards 'holy grail' of crystallography could help speed up the development of new medicines and treatments.

Here is how this Imperial College London news release summarizes the current status of protein crystallization.

Crystallisation is the process which converts materials, such as proteins, into three dimensional crystals, thus enabling their atomic structure to be studied. The three dimensional structure of the crystals indicates the proteins function, and from this, researchers hope to be able to develop more effective treatments.
However, production of high quality crystals has long posed a major bottleneck for X-ray crystallography. This problem has become increasingly acute with the advent of structural genomics and proteomics which aim to determine the structures of thousands of proteins. Protein crystallography plays a major role in this understanding because proteins, being the major machinery of living things, are often targets for drugs.

And here is a description of the technique developed by researchers from Imperial College London and the University of Surrey.

To direct the proteins to become crystals, researchers use a substance called a nucleant, which does this by encouraging protein molecules to form a crystal lattice.
The team, consisting of bio-medical scientists, material scientists and physicists, collaborated to develop a theory concerning the design of porous materials for protein crystallisation and put it into practice. The theory is based on the rational that the porous structure of a material, traps the protein molecules, and encourages them to crystallise.

Below is a "photograph under a light microscope of crystals of α-crustacyanin from lobster shell, growing on a bioactive gel-glass particle immersed in the crystallization solution" (Scale bar: 200 μm.) (Credit for image and caption: Imperial College London).

Proteins converted into crystals

This research work has been published online on January 6, 2006 by the Proceedings of the National Academy of Sciences under the name "Experiment and theory for heterogeneous nucleation of protein crystals in a porous medium." Here are some short excerpts from the abstract.

The determination of high-resolution structures of proteins requires crystals of suitable quality [and] the problem of crystallizing proteins is becoming increasingly acute.
There is therefore an urgent requirement for the development of new efficient methods to aid crystal growth. Nucleation is the crucial step that determines the entire crystallization process. Hence, the holy grail is to design a "universal nucleant," a substrate that induces the nucleation of crystals of any protein.

And here is a link to the full paper (PDF format, 5 pages, 312 KB), from which the above illustration has been extracted. Here are some of the conclusions.

The approach presented here to nucleating protein crystals on mesoporous materials has opened up a very promising avenue for protein crystallization. Two materials that are chemically very different, but have in common a wide pore-size distribution, have both been shown to be effective nucleants, whereas materials with minimal pore-size variation have failed.
Our theory and these experimental results suggest that it is desirable to have a disordered porous medium, one where the pores are highly nonuniform, because use of such a porous medium makes it likely that one or more pores will have very low barriers to nucleation.

Finally, here is how Naomi Chayen, professor at the Imperial College London, summarizes this advance in crystallography: "The first step in obtaining a good crystal is to get it to nucleate in an ordered way. The 'holy grail' is to find a 'universal nucleant' which would induce crystallisation of any protein. Although there has been considerable research in search of a universal nucleant, this is the first time we have designed one which works on a large number of materials."

Sources: Imperial College London news release, January 9, 2006; and various web sites

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