Nobelprijs Fysiologie of Geneeskunde 1999 voor de ontdekking dat eiwitten intrinsieke signalen hebben voor transport en lokalisatie binnen de cel

Abstract

The Nobel prize in Physiology or Medicine 1999 was awarded to Dr. Gunter Blobel for the discovery that proteins contain one or more signals in their structure that act as address labels. These are recognized by one of various transport machineries that direct the protein to a specific location in the cell, or into the secretory pathway out of the cell. His work joined traditional morphology and classic biochemistry in the notion of molecular topology, and led to the insight that proteins contain domains that specifically recognize domains in other proteins, nucleic acids, lipids et cetera. Specificity of recognition is provided by information that resides in the amino acid sequence of the domain. This work has had a great impact on pathophysiology as we now understand that malfunction of proteins may be due to incorrect localization in the cell, and thus due to a defect in transport and targeting. Typical example is the mislocalization of CFTR protein in cystic fibrosis. In a broader sense, malfunctioning of proteins often results from defective interactions with other proteins. The major challenge in the post-genomic era will be the unravelling of all signals that govern interactions between the 140,000 different proteins that are encoded in our DNA, to understand functions of these macromolecular interactions in the cell, and finally to trace and cure diseases that are caused by defective signals and interactions.