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 ...
