The Molecular Post Office Inside the Cell
- Date:
- May 15, 2006
- Source:
- Max-Planck-Gesellschaft
- Summary:
- For most proteins, there is a particular place inside a cell where they carry out their function. But how do they get there? Scientists from the Charité Berlin, the University of Heidelberg, and the Max Planck Institute for Molecular Genetics in Berlin have now been able to visualize the structure of a "molecular machine" involved in protein sorting using cryo-electron microscopy and single particle analysis.
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For most proteins, there is a particular place inside a cell where they carry out their function. But how do they get there? Scientists from the Charité Berlin, the University of Heidelberg, and the Max Planck Institute for Molecular Genetics in Berlin have now been able to visualize the structure of a "molecular machine" involved in protein sorting using cryo-electron microscopy and single particle analysis.
This "machine" is made up of a single active ribosome, plus a special signal recognition protein and a matching receptor. The scientists have shown that when the three proteins interact, certain areas open up on the ribosome, which allows the ribosome to dock onto another complex. The later complex, which is called translocon complex, takes over the job of transferring a newly produced protein through the membrane. Knowing the structure of the molecular machine helps scientists to understand how secretory and membrane proteins in a cell are expressed and sorted (Science, May 5, 2006).
Sorting proteins is fundamental to the gene expression of every organism - from bacteria to humans. Particularly important during biosynthesis is sorting secretory and membrane proteins, which have to find the way to their final destination inside or outside the cell. Secretory proteins are those that later on leave the cell, like anti-bodies. Membrane proteins are proteins embedded into the cell’s membranes - for example, signalling receptors. One particular molecular complex is important in protein sorting. It is made from an active ribosome - that is, the protein synthesis machine in the cell - called the signal recognition particle (SRP), and its corresponding receptor. It is the structure of this complex that the scientific team is now able to describe.
The key element to this machine's functioning is a signal sequence located at the N-terminal end of the protein to be sorted. The sequence acts as a kind of "postal code" in the cell. The SRP reads the sequence as soon as the newly built protein chain leaves the ribosome. The SRP binds to the ribosome and directs it, together with the SRP receptor, to what is called the "translocon complex" in the membrane of the endoplasmic reticulum. The translocon complex is made of a "protein conducting channel" and other membrane proteins. The ribosome is anchored at the translocon and continues with protein biosynthesis.
Notable is that the ribosome can no longer bind to the translocon as soon as the SRP has bound to the ribosome. The ribosome needs additional support from the SRP receptor, which it transfers from the SRP to the translocon. Now that scientists understand the structure of the complex, they can see how the receptor interacts with ribosome and SRP and replaces parts of the SRP molecule. In this way, specific sites are made available for the translocon, which allows it to bind to the ribosome. Understanding this key event during protein sorting is essential to understanding how secretory and membrane proteins are expressed in a cell.
The Berlin UltraStruckturNetzwerk (USN)
The UltraStrukturNetzwerk (translated, "ultra structure network") is a research network aimed at understand complicated "molecular machines" using the most modern of methods, including mass spectrometry and cryo- microscopy.
The USN, initiated by the Max Planck Institute for Molecular Genetics in co-operation with Charité; brings together more than 15 research groups in the Berlin-Brandenburg region. These groups come from the three Berlin Universities (Free, Technical, and Humboldt), the Max Delbrück Center for Molecular Medicine, the Leibniz Institute of Molecular Pharmacology, the University of Potsdam and the Max Planck Institute of Molecular Plant Physiology in Potsdam.
The USN has established the technological infrastructure to analyse molecular machines through the support of the European Union and the Senatsverwaltung für Wissenschaft, Forschung und Kultur Berlin, with a total contribution of 8 million euros. Core facilities are located at the Max Planck Institute for Molecular Genetics; they include a 300 kV Tecnai G2 Polara cyro microscope. The research presented in this article contains some of the first results from the network.
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