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ePaper created 2014-10-06, 17:11:00 | version 1.33.00
33 Proteins consist of amino acid chains and are vital components of the body. They serve as a tool in almost all activities of the human organism. During their synthesis in the cell, they undergo a complicated process that determines what shape they will assume and where in the body they will be deployed. What happens when a piece of this puzzle doesn’t fit right? Prof. Dr. Sabine Rospert and her team from the Institute of Biochemistry and Molecular Biology of the University of Freiburg made an astounding discovery in cooperation with colleagues from the USA: There is a mecha- nism in the cell that prevents the production of defective proteins before they can collect as waste material inside the cell. The origin of proteins, also known as polypep- tides, lies in the deoxyribonucleic acid (DNA) of the cell nucleus. Once the information stored for protein synthesis has been transcribed into mes- senger ribonucleic acid (mRNA), a sequence of so-called nucleotides, it leaves the nucleus and migrates through the cell to the ribosome, the site of the next stage in the process. This stage is called translation, and it is made possible by the ribosome complexes, which consist of large and small subunits. The mRNA makes its way in between the two subunits and passes on the code for synthesizing the polypeptide chain to a transfer ribonucleic acid (tRNA). Dynamic Event at the Tunnel Exit The nearly complete chain leaves the ribosome via a tunnel-like gateway in the large subunit. This is the site of a dynamic event. An assortment of protein biogenesis factors waits for the chain in order to bind to it and send it off in a complex interaction toward its destination, where it will be further modified. “We are studying many protein biogenesis factors, and each of them raises questions that we want to answer,” says Rospert. “It is clear that the factors can’t all bind at the same time, but which of them binds when and where?” It is known that each factor fulfills a specific function. Now the researchers want to understand how precisely each of these factors knows how its task is regulated. “How can it be that the factors are at the right place at the right time?” asks Rospert. The assorted protein factors waiting at the tunnel exit also include chaperones, which support the proteins in the folding process. “I would even go so far as to characterize these chaperones as midwives, because what they do is essentially to assist in the birth of the proteins.” One of the factors is a signal recognition particle (SRP). If it recognizes a particular signal sequence consisting of amino acids on the growing chain of a secretory protein – such as insulin – it attaches itself to the chain. In this way, SRP stops the translation process to ensure that enough time remains for the chain to bind to a receptor in the membrane of the endoplasmic reticulum (ER). The ER is a component of the cell in which the secretory proteins receive their final folding. The signal sequence splits off, and the receptor helps the protein reach the inside of the ER, where the final stage of its metamorphosis begins. It has long been known that every cell has a sophisticated quality control system at its disposal. Something can go wrong at each stage of protein biogenesis. In the case of misfolded proteins, the cell deploys a highly effective complex to rectify the situation: the proteasome. It serves as a waste bin for proteins that the control system has identified as defective or even toxic. However, the scientists are focusing on the interaction between the protein biogenesis factor “We asked ourselves what happens when the signal sequence of a secretory protein exhibits mutations.”