Protein Zip Code Discovery Leads to Nobel

Günter Blobel, a German-born Rockefeller University cell biologist described by colleagues as "the father of modern cell biology," has won this year's Nobel Prize in Physiology or Medicine. The Karolinska Institute's Nobel Assembly announced yesterday that Blobel was awarded the prize for his discovery that proteins come with "address labels" that determine their fate in the cell.

After proteins are synthesized in the cell's ribosomes, they have to travel to the place where they are needed. Some are transported to cell organelles like mitochondria or chloroplasts, while others are excreted to do a job outside the cell. In the early 1970s, Blobel suggested that the latter class--proteins scheduled for excretion--come with a stretch of amino acids at their tips that acts as a biochemical zip code. According to this "signal hypothesis," the code somehow helps guide the protein to the endoplasmic reticulum (ER), a vast, folded membrane system that looks like a deflated beach ball and was known to be a relay station for exported proteins.

In 1975, Blobel provided the proof for this theory by deciphering the first ER zip codes in an experimental setup that mimicked the cell's protein-sorting pathway. He and his colleagues then went on to decipher the ER's entire export system, including the "signal recognition particle" that recognizes the codes and the channel through which the proteins sneak into the ER.

Blobel, in various collaborations, later showed that similar zip codes serve to address proteins to all cell organelles and that these zip-code systems are found in all forms of life, from humans to bacteria. His work has shed light on diseases such as familial hypercholesterolemia and lysosomal storage disorders, which result from errors in the signals or the transport machinery. Protein signals have also become a crucial tool for researchers who genetically modify bacteria, plants, and animals to produce drugs. By adding a specific tag to the desired proteins, they can tag them for excretion, making them much easier to harvest.

Scientists in the field say they saw Blobel's prize coming. "This was long overdue," says cell biologist Randy Shekman of the University of California, Berkeley. "He nursed the entire [protein signal field] from the beginning to the end." Bernhard Dobberstein, a molecular cell biologist at the Center for Molecular Biology in Heidelberg, Germany, and Blobel's research collaborator in the mid-1970s, agrees. "Basically everything [Blobel] suggested has turned out to be true."