Mystery of protein synthesis solved

Five years ago x-ray crystallography made it possible for the first time to study ribosomes in cells, where the all-important synthesis of proteins takes place. But it hasnt been understood just how amino acids are joined together to form proteins. Now researchers at Uppsala University have discovered the only possible mechanism and have used it to explain a number of biochemical experiments.

The new findings, being published in the latest issue of Proceedings of the National Academy of Sciences, PNAS, are the answer to one of the hottest unsolved mysteries about exactly how protein synthesis takes place. The translation of the genetic code in the production of new proteins is one of the most central processes in living organisms. This takes place in the ribosomes of cells, which are large complexes of nucleic acids and proteins consisting of roughly a million atoms. After decades of biochemical research into how ribosomes function, major breakthroughs were made five years ago when American and British research teams managed to determine the detailed atomic structure of ribosomes with the aid of x-ray crystallography. This enabled scientists to see directly how the components needed for protein synthesis are arrayed three-dimensionally in the ribosome. Among other things, it was shown that none of the protein components participate directly in the chemical reaction in which amino acids are joined together, but rather that the reaction must by catalyzed by the ribosomes nucleic acids (RNA).

– This squares with the notion that there once was an RNA world, before our present-day, sophisticated enzymes had developed. In other words, it is believed that the ribosome, which is a primeval biological “machine”, might still show traces of this time, says Johan Åqvist, professor at the Department of Cell and Molecular Biology at Uppsala university.

The ribosome structure clearly showed how the genetic code is read, but the question remained how the catalytic process itself takes place, where amino acids are linked together to form new proteins. Using massive computer calculations, Johan Åqvist and doctoral student Stefan Trobro have now managed to simulate protein synthesis reactions and have examined several possible chemical mechanisms.

– Our findings show that there is only one possible type of mechanism, and we have been able give a detailed account of how it works and why the reaction proceeds so rapidly, says Johan Åqvist.

The theoretical calculations also serve to explain a number of biochemical experiments from recent years.