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Nobel for Blobel

By Sean Henahan, Access Excellence

Stockholm, SWEDEN (10/12/99)- This year's Nobel Prize in Physiology or Medicine goes to Günter Blobel, a pioneering cell and molecular biologist at Rockefeller University in New York. Dr. Blobel's research over the past 20 years has elucidated the nature of the molecular signals that determine the transport and localization of proteins in the cell.

There are about one billion protein molecules in every cell. Dr. Blobel identified universal signaling processes that are universal in yeast, plant, and animal cells. His work led to a key understanding of how larger proteins are able to move across the membranes of the organelles. He determined that newly created proteins were directed to their correct locations in the cell by identifying signals that act as a kind of cellular zip code.

"Günter made one of the most important discoveries in modern biology. A cell may have more than a billion protein molecules, all of which need to travel to a specific location. Through a historic series of experiments, Günter revealed that each protein has its own ‘molecular bar code,’ which the cell reads and then guides the protein to the correct location,"said Purnell W. Choppin, M.D., president of the Howard Hughes Medical Institute.

Dr. Blobel proposed the "signal hypothesis". Proteins exported out of the cell are synthesized by ribosomes, associated with the endoplasmic reticulum. The genetic information from DNA is transferred via mRNA. This information determines how the amino acids build up the proteins. First, a signal peptide is formed as a part of the protein. With the help of binding proteins, the signal peptide directs the ribosome to a channel in the endoplasmic reticulum. The growing protein chain penetrates the channel, the signal peptide is cleaved, and the completed protein is released into the lumen of the endoplasmic reticulum. The protein is subsequently transported out of the cell.

In 1980, Dr. Blobel described the general principles underlying the sorting and targeting of proteins to particular cell compartments. The protein itself carries the information that specifies its proper destination in the cell. These cellular zip codes, called topegenic signals, take the form of small amino acid sequences.

cell diagram Examples of directed transport mediated by topogenic signals. The figure shows a schematic cell with some of its compartments, the organelles. (A chloroplast is an organelle that is present in plant cells but not in animal cells). The organelles have special functions and they are surrounded by membranes. Newly synthesized proteins are provided with special "address tags", signal sequences or topogenic signals, which direct the proteins to a correct place within the cell and allow them to cross the membranes of the organelles. The signal itself consists of a chain of amino acids. It is an integral part of the protein, and it is often located at one end of the protein.

Dr. Blobel’s research continues to influence virtually all areas of biological research. His work laid the foundation for the discovery of the molecular mechanisms behind a number of genetic disorders. Cystic fibrosis, primary hyperoxaluria (kidney stone formation at an early age) and familial hypercholesterolemia ( very high serum cholesterol) all have been shown to have a a topogenic signaling cause.

"Dr. Blobel's work was seminal in our broad understanding of one of the essential parts of living systems--how molecular 'zip codes,' now known as signal sequences, target eukaryotic proteins to their proper intracellular destinations. Pioneering work in his laboratory is responsible for much of what we know about how proteins enter membrane-bound organelles. His work has led to an explosion of knowledge on the trafficking of proteins in the cell, and even on the way some kinds of drugs may be introduced into cells," said Marvin Cassman, Ph.D., Director of the National Institute of General Medical Sciences.


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