This week in Nature: new success for Professor Roland Beckmann in tracking down the cellular protein sorting machine Also involved: researchers from the University of Heidelberg, the Max Planck Institute of Molecular Genetics in Berlin and the University of Manchester
Professor Roland Beckmann is the head of a research group at the Gene Centre of the University of Munich investigating molecular machines in protein targeting and translocation. The work of the group revolves around the systematic transport of cellular proteins that have to be conveyed into or through membranes in order to arrive at their destinations. This highly complex process is essential in bacteria and also in the cells of higher organisms. Molecules and molecular complexes are involved in protein sorting and here it is necessary for the sorting signal to be recognised at an early stage in the ribosome. In the current issue of , Beckmann reports on his success in further elucidating the mechanics of this crucial structure. Also involved are researchers from Prof. Irmgard Sinning's team at the University of Heidelberg, the Max Planck Institute of Molecular Genetics in Berlin and the University of Manchester.
Proteins are the cell's most important functional units. Their structure is determined in the genes, i.e. certain sections of the DNA molecule. But frequently they can only perform their functions when they have reached their precise destination in the cell. The protein sorting process required for this is so important that the German-born biologist Günter Blobel (Roland Beckmann was a postdoc at his New York lab) was awarded the Nobel Prize for medicine in 1999 for his work in this area. One of the things he found out was that proteins that require sorting carry specific signal sequences. In higher organisms this sequence is found in anything up to one-third of the different proteins and is already present when the protein has not been fully synthesised. Accordingly, the sequence can already be read when the relevant protein is still connected with a ribosome, one of the cellular production sites for proteins.
At this point, the signal sequence is recognised by a molecular complex, the SRP or signal recognition particle, which then docks on. This has one major initial effect: protein synthesis stops. Ribosome and protein remain connected and are transported together by the SRP to a cell membrane. "In the long term," says Beckmann, "we want to understand the entire protein sorting process in bacteria and higher organisms. That is why we are investigating the complex molecular machines behind this process." In his previous work, Beckmann has successfully elucidated the structures of a number of complexes involved in protein sorting. In the latest article, he and his team explain some of the crucial interactions taking place in bacteria and eukaryotes.
The article presents various structures indicating the sorting signal first at the ribosome tunnel exit and then in the complex formed by active ribosomes with SRP. The remarkable thing about the study is that it shows both the bacterial and the eukaryotic complexes. In comparison with earlier studies, the resolution of the latter is so good that structural changes are identifiable in a part of the SRP that are a significant preparatory stage for the subsequent interaction with the SRP receptor. This detailed interpretation of the cryo-electron microscope data has been made possible by X-ray structural data from research groups like the one headed by Prof. Sinning. This shows how complementary techniques can be efficiently combined to produce impressive new results.
"Following the signal sequence from the ribosome tunnel exit to signal recognition particle", Mario Halic, Michael Blau, Thomas Becker, Thorsten Mielke, Martin R. Pool, Klemens Wild, Irmgard Sinning, Roland Beckmann, Nature, 29.10.2006
Prof. Dr. Roland Beckmann
University of Munich
phone: 089/218076900, fax: 218076999
For the Heidelberg contribution:
Prof. Dr. Irmgard Sinning
Heidelberg Centre for Biochemistry
University of Heidelberg
phone: 06221/544781, fax: 544790
Dr. Michael Schwarz
Press Officer of the University of Heidelberg
phone: 06221/542310, fax: 54317