New Details about the Molecular Post Room in Cells

A research group including the MPI for Molecular Genetics has succeeded in gaining new insight into the synthesis and sorting mechanisms for special proteins

Scientists from the Max Planck Institute for Molecular Genetics, the Ludwig Maximilian University in Munich and the University of Heidelberg have shown in previously unachieved high resolution new details of the complex biological protein sorting process in the cell. Using cryo-electron microscopy and single particle analysis, they have revealed for the first time in detail how newly formed protein chains are detected by a signal recognition protein when they leave the ribosome. The scientists have found that this process uses the same mechanism in bacteria as it does in more highly developed organisms [Nature, 29 October 2006, Advance Online Publication].

Sorting certain proteins in the cell and transporting them to their destinations are key stages in the functioning of all organisms. Most proteins are already assigned to the location where they are later used when they are biosynthesised. This is done with the aid of a molecular complex which consists of a ribosome, i.e. the protein synthesis machine in the cell and a signal recognition particle.

The key element for protein sorting is however a sequence of signals which is found at the start (called by scientists the n-terminal end) of the protein created from the ribosome and which functions like a postcode in the cell. The signal recognition particle (SRP) reads this sequence as soon as it leaves the ribosome at the start of a newly formed protein chain. In the next stage, SRP binds with the ribosome and with the participation of other components conducts it to the endoplasmatic reticulum (ER) where the next stages in the sorting process take place.

With a modern cryo-electron microscope made available by the Ultrastructure Network in Berlin, the team of scientists at the LMU in Munich, the University of Heidelberg and the Max Planck Institute for Molecular Genetics in Berlin have now been able to show at the molecular level, in previously unachieved quality, how the signal sequence of the SRP is recognised. The signal sequence, the "address" of the protein, binds to a special site on the SRP called the M domain. This bond results in rearrangement of the SRP itself, or in changes to its structure initiating the transmission of the signal sequence to the translocon complex (also see MPS press release [1]).

Around 30% of all the proteins in the more highly developed organisms, such as humans, for example, are sorted with this mechanism. This is particularly the case for secretory proteins, antibodies and membrane proteins, for example, which among other things act as receiver molecules for neuronal messengers or other signal molecules. This process is comparable in bacteria and in mammal cells. Its explanation is an important element in understanding the way in which secretory proteins or membrane proteins are passed on after they are formed in the cell.

Background information:

The Berlin Ultrastructure Network (USN)
The Ultrastructure Network is an integrated project with the aim of examining complicated "molecular machines" with the most advanced, leading edge methods such as mass spectrometry (MS) and cryo-electron microscopy (cryo-EM). The group was initiated by the Max Planck Institute for Molecular Genetics in collaboration with the Charité hospital and medical school in Berlin and now links more than 15 working groups in the Berlin-Brandenburg region. Members include the three Universities in Berlin (the Free University, the Technical University and the Humboldt University) along with the Max Delbrück Centre for Molecular Medicine, the Leibniz Institute for Molecular Pharmacology (FMP) and the Max Planck Institute for Molecular Plant Physiology in Potsdam.

Funded by the European Union and the Berlin Senate for Science, Research and Culture (8 million euros in total) the technological infrastructure required for the analysis of "molecular machines" has been set up in the Ultrastructure Network. The core facilities, including a 300 kV Tecnai G2 Polara cryo-electron microscope, are located at the Max Planck Institute for Molecular Genetics. Localising the signal sequence in the active ribosome and in the various ribosome SRP complexes is one of the first research results achieved during the developmental phase of the USN.