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.
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.
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. Blobels 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.