How to fold proteins?

Proteins are among the most important building blocks of life. To function properly within the body, their amino acid sequence needs to be folded into a defined three-dimensional structure within each cell. When this highly complex folding process fails, severe diseases such as cancer, Alzheimer’s or Parkinson’s can be the consequences.

For a long time, biomedical researchers tried to understand how folding proceeds in detail. One of these questions was how folding helper enzymes work. For parvulins at least, one group of folding helper enzymes, new answers are at hand given by scientists from the Centre for Medical Biotechnology (ZMB) of University of Duisburg-Essen (UDE), Germany. Drs Peter Bayer and Jonathan W Mueller succeeded in visualising single hydrogen atoms within the core of highly diffracting crystals of the parvulin protein Par14. Their study was published in the Journal of the American Chemical Society.

Among others, folding helper enzymes of the parvulin type are responsible to fold and maintain proteins in their native three-dimensional structure. Though profound knowledge exists on structure and mechanism of these enzymes, the role of individual amino acids in the catalytic core of parvulins remained unknown to date.

Hydrogen atoms are extremely small and hence normally invisible to the X-ray eye when investigating proteins. Within the core of the protein Par14, however, they could be visualised in corporation with scientists from University of Bayreuth.

„This has helped us enormously. We could realise an intricate network of hydrogen bonds that connects different amino acids within the core of the protein,” Dr. Mueller says. If one of these amino acids is replaced by another protein building block, catalytic activity nearly completely vanishes. This is first proof that an extended network of hydrogen bonds is a central feature of parvulin-type folding helper enzymes.

Further information:

Drs. Peter Bayer and Jonathan W. Mueller, phone +49-201/183-4676, peter.bayer@uni-due.de, www.uni-due.de/biochemie

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