Secondary structure adventures with Carl Woese

Not long after my arrival at UCSC as an assistant professor, I came across Carl Woese's paper Molecular Mechanics of Translation: A Reciprocating Ratchet Mechanism.(1) In the days before the crystal structure of tRNA was known, Fuller and Hodgson(2) had proposed two alternative conformations for its anticodon loop; one was stacked on the 3 ' side (as later found in the crystal structure) and the other on the 5 ' side. In an ingenious and elegant model, Woese proposed that the conformation of the loop flips between Fuller and Hodgson's 5 '- and 3 '-stacked forms during protein synthesis, changing the local direction of the mRNA such that the identities of the tRNA binding sites alternated between binding aminoacyl-tRNA and peptidyl-tRNA. The model predicted that there are no A and P sites, only two binding sites whose identities changed following translation of each codon, and that there would be no translocation of tRNAs in the usual sense-only binding and release. I met Carl in person the following year when he presented a seminar on his ratchet model in Santa Cruz. He was chatting in my colleague Ralph Hinegardner's office in what Carl termed a Little Jack Horner appointment (the visitor sits and listens to his host describing What a good boy am I). He was of compact stature, and bore a striking resemblance to Oskar Werner in Truffaut's film Jules and Jim. He projected the impression of a New-Age guru-a shiny black amulet suspended over the front of his black turtleneck sweater and a crown of prematurely white hair. Ralph asked me to explain to Carl what we were doing with ribosomes. I quickly summarized our early experiments that were pointing to a functional role for 16S rRNA. Carl regarded me silently, with a penetrating stare. He then turned to Ralph and said, in an ominous low voice, I'm going to have some more tanks made as soon as I get back. Carl's beautiful model was, unfortunately, wrong-it was simpler and more elegant than the complex mechanism that Nature actually uses. Unyielding, Carl railed against the A-site-P-site model at every opportunity,(3)(,)(4) and although we ended up enjoying a long, intense, and fruitful collaboration, and became close, life-long friends, I finally gave up trying to describe to him our biochemical and crystallographic results on the A, P, and E sites.