The mighty, mighty ribosome

Life starts with the ribosome: the tireless maker of tiny machines, and my third structure of Christmas.

All the myriad things our bodies do are carried out by tiny biological machines – proteins, mostly – each of which has a specialised function: move muscle, sense light, send message, make tiny machines…

Proteins are profoundly beautiful. Picture it: an ordered set of amino acids like any other polymer, except that evolution has found the precise arrangement to make it into a functioning, three-dimensional machine. Quite a lot of a cell’s energy is spent on manufacturing proteins, using one of the largest, most complex bits of machinery we have: the ribosome.

The machine burger

A ribosome has two major parts that fit together, like an unbalanced hamburger bun, with one side much bigger than the other. Each side is made from one or two strands of RNA and a small squadron of proteins (in our 3D model, the RNA is blue-grey, the proteins are green). The two clamp over a messenger RNA (a fresh copy of part of the genome), so that it kind of looks like an unbalanced hamburger with a very long piece of bacon poking out on either side.

This messenger RNA (mRNA, the bacon) is what encodes the order of amino acids for each protein. Each type of protein has a different mRNA: a copy of a different section of DNA somewhere on the genome.

How it works

While it might look like a sloppy hamburger, the ribosome actually acts more like a knitting machine, taking in long strands of nucleotides and translating them into amino acids, which then fold up into precise shapes.

Proteins are made up of different combinations of the 20 different amino acids, but the instructions are written in a language with only four letters (DNA or RNA nucleotides). The ribosome reads those instructions, and constructs the protein.

To do this, it reads groups of three nucleotides at a time – triplets of RNA bases. In each of the 64 possible triplets there is one specific transfer RNA (tRNA) – will have the mirror image of the mRNA triplet on one end and the ‘right’ amino acid on the other. The tRNAs come to land on the ribosome and the ribosome checks this mirror-image pair (called a codon–anticodon pair) on its ‘landing pad’ – where that bottom part of the bun sticks out.

If everything checks out, the ribosome ‘flips’ that amino acid on the end of the tRNA (forming a tough chemical bond) , adding it to the protein chain. Then it moves on. The entire ribosome moves down three nucleotide positions on the mRNA, and repeats the process.

So where does a protein ‘start’ and where does it ‘end’? There is a “start here” signal at the beginning, and one of three special triplets in the mRNA indicates when the protein ‘ends’. Thousands of these machines in each cell line up, one after the other, on mRNAs from the genome, producing the machines of life.

I like to imagine them making quite loud, clunk-shift-weld noises with each step, some of the biggest proteins in our cells working away.

True form

Knowing the structure of the ribosome and understanding how it works are, understandably, hugely important to biologists. However, given how huge the ribosome is, its structure was not easy to work out.

It had to be worked out bit by bit, and the challenge of piecing the components together was compounded by the need to separate the ribosomes from everything else (mRNA, other proteins, bits of cells etc.) without making them fall apart. The ribosomes were very difficult to see on their own, even if one could get them into reasonably pure shape.

Early electron microscope pictures gave a sense of the overall shape of the ribosome (the hamburger with some curious bulges and clefts). But after years of painstaking work, the methods were there for crystallising certain types of ribosomes successfully. At first they were not the best of crystals, but the resolution improved steadily and the scientists who won Noble prizes for the structure of the Ribosome (Venkatraman Ramakrishnan, Thomas Steitz and Ada Yonath) solved this massive complex.

A heart of RNA

The ribosome is a behemoth structure, with its three or four RNAs, nearly 80 proteins and 200,000 atoms in total. It has hundreds of oh-so-carefully poised facets to create the interfaces between proteins and RNA, and between proteins and other proteins.

The real surprise was that the RNA components of the ribosome are not merely the scaffold, or a bit extra – they are the very core of the ribosome, snaking their way into the heart of the action, where the amino acids are conjoined.

The original innovator

The structure of the ribosome and the central role RNA plays in it provided the keys to understanding another burning question: how did life start? If ribosomes are tiny machines that make other tiny machines, then what made the first tiny machine?

‘Life’ almost certainly did not start off as proteins, but rather RNA. RNA stores information, like DNA, but it also folds up into specific shapes, like proteins and can catalyses chemical reactions.

The start of life could well have involved a self-replicated piece of RNA that carried around its genetic information and acted as the business end of a super-primitive living entity. Over time, the successful RNAs evolved to extend their chemistry by making proteins and ‘backing up’ their genetic information into DNA: its more stable, boring chemical cousin.

The RNAs in the ribosome are the direct descendants of these early RNA innovators, those that extended the chemistry of the RNA world into proteins. Every single living cell on our planet has these molecules, tirelessly toiling away to make the proteins that give us life.

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