How proteins find their destination
The Institute of Molecular Biology and Biotechnology of FORTH participates in the effort to understand a fundamental biological problem: How do cells regulate trafficking of their proteins? Some of the research results are presented in a recent publication in Cell, one of the most authoritative international scientific journals. They stem from intercontinental cooperation between the research teams of Charalambos Kalodimou, Assistant Professor at Rutgers University (New Jersey, USA) and that of Tassos Economou, IMBB researcher and Associate Professor at the Biology Department of the University of Crete.
Thousands of proteins are produced inside our cells. One third of these proteins can fulfill their function only after migrating to the outside of the cell, becoming anchored to the cell membrane or target specific subcellular compartments. These processes are essential for life. That is why compromised targeting of certain proteins leads to pathological conditions such as the hereditary disease cystic fibrosis and several autoimmune diseases. Examples of migrating proteins are insulin, antibodies, membrane channels and toxin-proteins secreted by pathogenic microorganisms.
How do migrant proteins find the way to their final destinations and how do they go through cell membranes? More than 30 years ago, Nobel Prize winner Gunter Blobel from Rockefeller University, New York, discovered that migrating proteins contain chemical signals called leader peptides. These peptides have a double function: they act like postal addresses as well as like miniscule handles. Depending on its final cellular destination, each migrating protein bears a different address. The Kalodimos / Oikonomou labs have now demonstrated the precise mechanism through which a specific cellular receptor first binds the migrating proteins on the membrane surface and subsequently leads them through the membrane in a sewing-machine fashion. These observations were made possible, through the use of innovative methods of structural biology developed by the Kalodimos team.
The discovery of this key biological mechanism is expected to help improve our understanding of protein trafficking disorders and provide better means of treating diseases caused by it. It is also expected to help develop new antibiotics against pathogenic bacteria. Finally, it offers the possibility to optimize the biotechnological production of human biopharmaceuticals using microbial cell-factories. The pursuit of these research directions as well as the further exploration of subcellular protein trafficking at IMBB is funded by European and American grants, the General Secretariat of Research and Technology and the pharmaceutical company Pfizer.
For more information please contact:
Tassos Economou, IMBB Researcher
Tel. & Fax: +30 2810 391166
Babis Kalodimos, Assistant Professor, Rutgers University, Dept of Chemistry
Tel: +1-973-353-5457, Fax: +1-973-353-1264