Transfer RNA Model, 1975
In 1965, Cornell biochemist Robert Holley deciphered the 77 nucleotide sequence of transfer RNA. Three years later, Holley was awarded the Nobel Prize for this work, but already the race to determine tRNA’s three-dimensional structure was in full swing. At least six laboratories around the world tried various x-ray diffraction techniques, but the small, amino acid–carrying molecule did not crystallize very well under standard procedures.
Alexander Rich, a biophysicist at the Massachusetts Institute of Technology, was the first to devise a solution. Rich and his MIT colleagues added the chemical spermine, which stabilized tRNA’s folding. This technique allowed them to prepare high-resolution crystals from yeast phenylalanyl tRNA and image them using x-ray diffraction. In December 1972, the MIT team announced the shape of that tRNA molecule at 5.5 Å resolution, revealing the outlines of the molecule but not the surface detail. A month later, they had the resolution down to 4 Å, and they could see a novel L-shaped folding of the polynucleotide chain and the overall cloverleaf configuration.
The chain folding came as a complete surprise. Scientists had all sorts of ideas about the shape “but all of the earlier guesses proved incorrect,” Rich says. A year later, Rich’s team and a group led by Aaron Klug at the Laboratory for Molecular Biology in Cambridge, United Kingdom, independently defined the structure at even greater resolution.
In order to solve the structure, Rich constructed a physical model of tRNA to accurately fit the experimental diffraction data. In January 1975, through a unique MIT program to involve undergraduates in research, he hired a freshman student, Elizabeth Cavicchi, who helped build a wire model (shown here) that stood about 1.2 m high, 1.5 m wide, and 0.75 m deep—the scale determined by the size of the wire atoms. “I still think of this model as my first sculpture,” says Cavicchi, now an MIT instructor in science education.