Blobel's Nobel A Vision Validated

cytoplasm, and serves as an adaptor to couple the ribo-1980, the year that Christiane Nusslein-Volhard and Eric some to the membrane-associated translocation ma-Wieschaus embarked on their Nobel Prize–winning chinery in the rough ER. screen for embryonic lethal mutants in Drosophila, in The truly amazing aspect of all this is that a quarter some ways marked the end of the Age of Beautiful Theo-century of experimentation by Blobel and his colleagues ries in biology, and the dawn of the Age of Ugly Facts has over and over again validated the basic concepts of (to paraphrase T. H. Huxley, whose view of a tragedy the original signal hypothesis: secretory and membrane was " a beautiful theory murdered by an ugly fact " *). If proteins indeed contain short stretches of hydrophobic Watson and Crick's double-helical model of the struc-amino acids that target the polyribosomes synthesizing ture of DNA showed that imagination (with a sprinkling them to the rough ER, and in most cases these are at of data) could triumph over Nature, Nusslein-Volhard the amino terminus as originally predicted; there is a and Wieschaus's saturation mutagenesis showed that specific receptor for such " signal peptides " ; and recog-evolution can produce biological mechanisms of such nition of the signal peptide and docking of the polyribo-unimaginable complexity that it would be useless, if some to the rough ER opens a proteinaceous tunnel in not laughable, to try to intuit them a priori. Nature's the membrane that facilitates translocation of the na-imagination, it showed, usually far outstrips that of the scent chain across the lipid bilayer. Furthermore, the human brain. The Awesome Power of Genetics com-concept that variations in the number and the position-bined with Molecular Biology had created a way to solve ing of signal sequences within the polypeptide chain biological problems while making as few assumptions could be used to explain the " stitching " of membrane as possible, let alone having to construct hypotheses proteins of various topologies in and out of the lipid out of whole cloth. bilayer, laid out in another theoretical paper entitled Gü nter Blobel proposed his astonishingly bold " Signal " Intracellular Protein Topogenesis, " has proven largely Hypothesis " together with David Sabatini in 1971, on correct as well. Finally this basic model, originally formu-the cusp of this paradigm shift in Experimental Biology. lated to explain the targeting of secretory and membrane It was sheer …