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TMV: the biological role of the two-layer disc


TMV: attempting to crystallise the A protein
Aaron Klug Scientist
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Ken Holmes was working to solve the structure of the whole virus.

[Q] Yes.

And I wondered if it was going to be possible to get to a high resolution. So as a companion I thought that we would be trying to crystallise some of the substructures that are found when you try to extract TMV protein, that is the sub-unit protein on its own. And I thought that might be possible to crystallise what was thought to be a trimer... this is a trimer of the TMV protein, the so called 'A protein'. The... so I... Reuben Leberman was with us and he was preparing large quantities of virus for... for the X-ray work on the intact virus. But the... I... I found... I... I read all the original papers of Schramm that started off the early work on viruses in Tübingen in Germany and saw that under certain conditions you'd got quite a large proportion of so-called A protein, which was thought to be a trimer, in fact its aggregate with something between two and five or two and five units. And I thought that that might crystallise, so... I asked Reuben... Reuben Lieberman to... to make large quantities of this and set up a crystallisation. And he produced the... indeed it did form crystals, but, the crystals had very large unit cells, several hundred angstroms. And before, we knew what it was; it was clearly some large aggregate. Now, Don Caspar, who we mentioned before, had talked a great deal about... sub... he'd written a paper about sub-assemblies of TMV which is rather an exercise theoretical physical chemistry. There wasn't much data in what he analysed but it was... he had some idea that the sub-assemblies may be important in the assembly of TMV. So what happened was that the crystal structure was... we found, in the early '60s, I've forgotten when it was, that the fact that this... this was a crystal not of the... not of the trimer of the TMV protein but the crystal of a ring-shaped unit. And you could see from the X-ray diffraction pictures which were obtained by yourself, John, and also by Chang, who was visiting... from China, that they had 17-fold symmetry. And these... these clearly consisted... so the crystals, the unit cell was huge... it contained... rings of protein, 17 units in the ring and two rings stacked together which we called the disc, the two-layered disc. Now, this was... something like this had been described by Norman Simmons and other people working with the chemistry of the TMV proteins, quite a lot of people were working... TMV was used by many different people for different objects and TMV was a hard source of protein. So you'd do physical chemistry and Lauffer for example was measuring the specific volume and finding out the hydration of protein. TMV was a work horse in many different parts that we now call structural molecular biology, including the genetic code as far as the TMV RNA is concerned.

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: Reuben Leberman, Don Caspar, Norman Simmons

Duration: 3 minutes, 47 seconds

Date story recorded: July 2005

Date story went live: 24 January 2008