In the cellular city, there is one factory which reigns supreme and it is called the ribosome. This is the molecular factory which produces proteins. It is a monolithic molecular complex which literally “translates” the information in genes (encoded by sequences of DNA and RNA) into proteins. It is also very ancient and is found in all forms of life on the planet including all bacteria, plants and animals (and us). The “translation” is very complicated because is really more than translation. For example, if I were to translate some instructions from one language to another (say Danish to English) I’m not really changing the instructions – I’m simply representing them in a different language. But if I were to translate the instructions to build a house from Danish to English and then follow this by building the house, then I have transformed the instructions into something which is much, much more than words on a page. This is what the ribosome does. It takes the instructions written in the DNA and RNA and builds proteins which are the workhorses of the cell doing everything from digesting our food to combating invading bacteria. Here’s a cartoon of the ribosome in action:
Before 2000, what we knew about the ribosome structure was not a great deal more than the blob in this cartoon. Can you imagine going to the middle of a great city to look at its most important factory and just seeing the bland exterior walls? You might see components being delivered at one end and the finished products being taken away at the other end, but you have very little idea about how the factory works. And you’re a scientist, so knowing how things work is kinda important. In 2000, several scientific groups radically changed this view and took us from the outside looking at the walls, to the inside of the ribosome, where we could see every atom and all the machinery (including every nut, bolt and screw) which makes proteins in all cells.
For this work, three people won the Nobel Prize in Chemistry this year. As an aside, there was some surprise that a dramatic leap in biology should be awarded a prize in Chemistry. To which one of the laureates replied… “…when you look at any biological question it becomes a chemical problem…”.
The structure of the ribosome is also a great story and I was reminded about this by the public release of several original papers published by one of the Nobel Laureates, Ada Yonath. These papers were published in the Journal of Molecular Biology in the 1980s and early 1990s and have been made open access. These papers are sufficiently old that they are only available as large pdf files, but if you want to download them here is the address. The first paper (from 1984) shows some tiny crystals and pictures of “X-ray diffraction patterns” for a large chunk of the ribosome. This paper is reminiscent of the X-ray diffraction patterns recorded by Maurice Wilkins (a New Zealander) and Rosalind Franklin in the early 1950s which led Watson and Crick to propose the double helical structure of DNA.
In coaxing large pieces of the ribosome to crystallise, Ada Yonath was attempting something outrageous. In the 1980s, if you were able to crystallise a single small protein and determine its 3-dimensional structure using X-ray diffraction, you could publish the structure in the most prestigious journals. But here was Ada Yonath and her colleagues attempting to crystallise an enormous molecular complex made up of 31 proteins bound to a large RNA scaffold. Yonath and her group were not the first to finally determine the structure of the ribosome, 15 years later (just as Wilkins and Franklin were not the first to determine the structure of DNA), but it was Yonath’s tenacious and audacious work in purifying and crystallising ribosomes from weird bacteria which paved the way for others to show us the nuts and bolts of proteins synthesis. A new view which is fantastic in its complexity and which is common to all of life on earth.