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Creating modern structural molecular biology


Competition to solve the structure of tRNA
Aaron Klug Scientist
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We solved the structure of tRNA, Jane, by this time John Robertus, a Post Doc from the States had joined us and also Jane...

[Q] Ladner.

Jane Ladner, yes, but she had... her maiden name was... she was really Jane Ladner by this time. And she had... And she grew... she actually succeeded in growing good crystals, four-, three-dimensional crystals of tRNA. She was actually trying to grow a mixture, I mean a tRNA with something else but it... what happens, one of the species crystallised out, she was trying to see interactions between them. And so John Robertus and you, John... solved the crystal structure, didn't you? And John Robertus who had come to do something else.

[Q] Yes.

He had been... he had been a, he'd been trained as a psychologist but he wanted to go into chemistry... because he found psychology too frustrating. He was a very active fellow. And so the first crystal structure was published in 1974. Now, we were competing with Alex Rich, who was working on the very same... very same... species of tRNA. And he was a fast follower and he... and they had... they had an orthorhombic from; we had monoclinic form, which is simpler in some ways. Of course, there were troubles about the heavy atoms, I won't go into all the troubles, but, it took... until, I think Jane's crystals were published in 1972 and it took till '74 to solve it. I won't go into all the technical details of that. And the structure was a three dimensional folded structure, it had all sorts of interesting... non-Watson-Crick bases and so on. Alex Rich, thought he would steal a march on us... he published a paper at four angstroms, sometime ahead and he totally misinterpreted the map. They were... they because it was low resolution but they didn't understand that they actually were... the backbone of the molecule they traced went through certain base pairs and they got it all wrong and our paper was right. But he managed to... he managed to tell the world that they had done it at the same time, which wasn't true at all. It was a conference that went on in Madison and so on. I wasn't there but John Robertus and Brian Clark were there and they weren't quick witted enough to see that what he was presenting was our structure, not his. Anyway, so there's quite a lot of... quite a lot of unpleasantness in science. When I charged him with it on the telephone, he said to me, 'I'm not a saint'. He's not a saint, doesn't mean to say you're not a sinner.

[Q] Sung Ho Kim.

Yeah... Sung Ho Kim well... yeah, that, I didn't want to go into that whole story, Sung Ho Kim whatever happened... they disagreed about the high resolution model. Sung Ho Kim actually got it right but Alex preferred to... he had left Alex but the... Alex had worked with a chap who went... went to Alabama whose name I'll remember in a moment; And Alex published... the wrong choice. They couldn't... the map wasn't clear enough to see the chain tracing and they choose the wrong one. But it's really quite cunning, in the model he shows that there's a certain base pair of 1538, a non-Watson-Crick base pair, as some people described these GC non-Watson-Crick. And I knew the model had to be right because you, in many tRNAs you had AT and GC but never switched chains, so it had to be a non-Watson-Crick, not like this but like this, this is the glycosidic bond. So I knew that was right, I remember showing it to Francis and he said, 'Oh, it must be right.' But Alex, in the text, in the models he pub... in the text he says: later on it could also be the other way round, you see, covering his tracks. So that was tRNA.

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: John Robertus, Jane Ladner, Alex Rich, Brian Clark, Sung Ho Kim

Duration: 4 minutes, 26 seconds

Date story recorded: July 2005

Date story went live: 24 January 2008