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Producing a phase diagram for the A protein


TMV: the biological role of the two-layer disc
Aaron Klug Scientist
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Norman Simmons and others had described in infected plants, sometimes saw ring like objects. You couldn't see the exact structure of this but if you took a leaf of an infected plant and simply put it into a negative stain you could see these ring-like structures. And although I don't think you could see that there were 17 units in this ring... which you could deduce from the X-ray work, it was clearly something very similar. Now, people dismissed this or... said that the... this is an example of a sticky protein and this could be... but Don Caspar, who had held the view that they might be intermediates in the assembly. I took it seriously and I thought that, maybe it's... maybe it's... relevant, it is relevant, and Don Caspar was right, that's relevant to the assembly. And then I remembered the model of Tobacco Mosaic Virus we built in 1958 for the World's Fair, Ken, the two of you were involved in that. And if you remember, what we did was to get some units made of polystyrene. Rosalind Franklin had been invited to exhibit in the World's Fair and we exhibited a model of Tobacco Mosaic Virus and a model of a spherical virus; that was the... which had icosahedral symmetry. So we made things out of polystyrene, I got a sculptor friend of mine, an impoverished sculptor friend to make these things out of polystyrene... and get the right shapes. And in the case of Tobacco Mosaic Virus, we made the shapes, and if you remember, the shapes didn't quite fit, so when they were being assembled into helical structure, it built out like a flower instead of building up a rod. Yes. And then you and... I think we sat up all night before it was assembled, in Brussels, filing away the surfaces so they would all fit perfectly; it was a great rushed job. But the... now the point about that, in order to get that started I realised it was very hard because we had... the idea was: this is Tobacco Mosaic Virus, this is before the discovery of the disc, we had to start... we had to start the assembly, so I got Ernie, Ernest as his name was, to build a little helical ramp on which we could put the sub-units in... into a turn of a helix to start off the assembly. And then we... the TMV RNA was in the form of a plastic pipe, a red plastic pipe; the model is still on the stairs... here in the lab. And the... And we built a complete, almost a complete turn to start off and then we started adding the units in to assemble it. So we build a... a nucleation site, a little scaffold to start the assembly. And then, somehow or other, the penny dropped and I don't know at which point it happened but remember I referred to the phase change in steel. I'd done my PhD on nucleation and growth and I suddenly realised that in order to get such a complicated object built you needed to nucleate it. And maybe this two layer disc was the... the equivalent of this helix with which you would start putting the RNA down onto the surface of this two-dimensional disc. So it wasn't a... it wasn't just a... an adventitious object which happened to... probably a sticky probe but maybe it had a biological role. And there were lots of them. Now, I didn't at the time think that we were going to get involved with physical chemistry, but I did go to speak to a meeting at which Don Caspar was there. Robley Williams out of the TMV people, Norman Simmons and I proposed that this would be... this disc would act as a nucleation for the growth of the virus, I remember saying that. It was poo hoo'd but nobody took it up. And then I began to wonder whether, you know, under what circumstances the disc existed because Reuben had crystallised it under high salt conditions; so I decided... and this was done with Tony Durham, was it?

[Q] Yes.

And we'd had a new research student, who joined the lab. Who did the phase diagram?

[Q] It was Tony Durham.

Tony Durham.

[Q] Yes.

And so I... I got him to study because he was a research student and he was very keen and he had a good record. And I said, 'We ought to find the states of aggregation in the TMV protein.' You see, Don Caspar who'd proposed this never got round, ever, it was very characteristic, never got round to actually to studying these things. He would... he... he had a knack of avoiding the, not the difficult problems but the main... the main line problem.

Born in Lithuania, Aaron Klug (1926-2018) was a British chemist and biophysicist. He was awarded the Nobel Prize in Chemistry in 1982 for developments in electron microscopy and his work on complexes of nucleic acids and proteins. He studied crystallography at the University of Cape Town before moving to England, completing his doctorate in 1953 at Trinity College, Cambridge. In 1981, he was awarded the Louisa Gross Horwitz Prize from Columbia University. His long and influential career led to a knighthood in 1988. He was also elected President of the Royal Society, and served there from 1995-2000.

Listeners: Ken Holmes John Finch

Kenneth Holmes was born in London in 1934 and attended schools in Chiswick. He obtained his BA at St Johns College, Cambridge. He obtained his PhD at Birkbeck College, London working on the structure of tobacco mosaic virus with Rosalind Franklin and Aaron Klug. After a post-doc at Childrens' Hospital, Boston, where he started to work on muscle structure, he joined to the newly opened Laboratory of Molecular Biology in Cambridge where he stayed for six years. He worked with Aaron Klug on virus structure and with Hugh Huxley on muscle. He then moved to Heidelberg to open the Department of Biophysics at the Max Planck Institute for Medical Research where he remained as director until his retirement. During this time he completed the structure of tobacco mosaic virus and solved the structures of a number of protein molecules including the structure of the muscle protein actin and the actin filament. Recently he has worked on the molecular mechanism of muscle contraction. He also initiated the use of synchrotron radiation as a source for X-ray diffraction and founded the EMBL outstation at DESY Hamburg. He was elected to the Royal Society in 1981 and is a member of a number of scientific academies.

John Finch is a retired member of staff of the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK. He began research as a PhD student of Rosalind Franklin's at Birkbeck College, London in 1955 studying the structure of small viruses by x-ray diffraction. He came to Cambridge as part of Aaron Klug's team in 1962 and has continued with the structural study of viruses and other nucleoproteins such as chromatin, using both x-rays and electron microscopy.

Tags: World's Fair, Norman Simmons, Don Caspar, Robley Williams, Rosalind Franklin, Tony Durham

Duration: 5 minutes, 8 seconds

Date story recorded: July 2005

Date story went live: 24 January 2008