Behind the picture: An early model of the ribosome
The MRC National Institute for Medical Research (NIMR) turns 100 this year and its rich history is fertile ground for looking back on past discoveries. This 1960s molecular model represents an important point in the evolution of thinking about the structure of the ribosome. Katherine Nightingale spoke to Dr Bob Cox about constructing the model ― and getting a few giants of biomedical research to sign it too.
Look closely at one of these polystyrene balls and you’ll find the autograph of one of science’s most celebrated sons, Francis Crick. As well as being part of the duo that discovered the structure of DNA, Crick also proposed the “central dogma” of molecular biology: that DNA makes RNA makes protein. Fitting then, that his signature is here on an early model of the ribosome, the molecular machine that makes proteins.
Ribosomes are cellular factories made of RNA and protein which ‘translate’ the genetic code into the corresponding amino acid code, specific to each protein. They are large and complex molecules, made up of around 50 proteins divided into two subunits. They were discovered in 1955, though they didn’t get their name until 1958.
This model, produced by NIMR researcher Bob Cox in 1969, was the first attempt to model ribosome structure in detail. Until then, only blurry microscope pictures had been available.
Researchers knew that ribosomes were made of proteins and RNA. The only other similar structures known at the time were viruses, which are DNA or RNA packaged inside an envelope of uniform proteins. But Bob knew that ribosomes were made up of lots of different types of proteins. “The question was how could all these proteins fit together with RNA to make a molecule that made some kind of functional sense?”
In Bob’s model the main structure is RNA ― represented by twisting copper wire ― bound to a range of proteins (the white balls). The small tags attached to the wire stand in for the RNA’s nucleotides. The distinctive folds in the wire form specific binding sites for proteins, and the arrangement means that the RNA is accessible to play its role in protein synthesis.
“Because each ball represents a different protein, I had a bit of fun and asked people to sign them,” says Bob. “They would laugh and say ‘one day it’ll be worth a lot of money.’” Other signatures on the model include giants of biomedical research such as Peter Medawar, John Kendrew, Arthur Kornberg and Marianne Grunberg-Manago.
The model was made in the NIMR’s workshop by Frank Doré. “He deserves considerable credit for putting the model together,” says Bob. The larger subunit has around 3,000 tags and the smaller subunit 1,500. Bob himself made an earlier version from dowling and wire.
The detailed structure of the ribosome wasn’t solved until the early 2000s, for which MRC scientist Venki Ramakrishnan won the Nobel Prize for Chemistry in 2009. Like Bob’s model, it shows two irregular shaped subunits, each with distinctive protuberances. It also shows interactions between distant segments of RNA, as well as the short range interactions shown in the model.
But for Bob, his model represents a good first stab at a structure, just a decade after the ribosome was first named.
“I would talk about [the structure] at meetings and take the model with me and no one laughed at it, so there was a feeling that though it might not be right it was a good start.”