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Proteomics - protein separation

The Crick Papers: 1955 From DNA to protein

1/3/03. By Giles Newton

Crick predicted the existence of 'adaptors', later found to be transfer RNA.

There were still uncertainties about the relationship between nucleic acids (DNA and RNA) and proteins. In a 1955 note to an unusual organisation, 'The RNA Tie Club', Crick predicted the existence of 'adaptors' that would transfer the information from the RNA template into the amino acid sequence of the protein.

This idea was soon shown to be true; the adaptors in protein synthesis being transfer RNAs. Crick describes the 1955 RNA Tie Club note as his 'most influential unpublished paper' - a full copy of which is presented in the online gallery below.

"Meanwhile [George Gamow], in his typical way, had founded that unusual organisation, the RNA Tie Club. There were to be only twenty members, one for each amino acid, and not only did each member receive a tie, made to Gamow's design by a haberdasher in Los Angeles, but also a tie pin with the short form of his own amino acid on it. I think I was Tyr but I'm not sure I ever got the tie pin. As it turned out the club served as a mechanism for circulating speculative manuscripts to the few people interested."

Crick, 'What Mad Pursuit' (1988), 95.

DNA
From DNA to protein
On degenerate templates and the adapter hypothesis: a note for the RNA Tie Club, 1955

"The main idea was that it was very difficult to consider how DNA or RNA, in any conceivable form, could provide a direct template for the side-chains of the twenty standard amino acids. What any structure was likely to have was a specific pattern of atomic groups that could form hydrogen bonds. I therefore proposed a theory in which there were twenty adaptors (one for each amino acid), together with twenty special enzymes. Each enzyme would join one particular amino acid to its own special adaptor. This combination would then diffuse to the RNA template.

An adaptor molecule could fit in only those places on the nucleic acid template where it could form the necessary hydrogen bonds to hold it in place. Sitting there, it would have carried its amino acid to just the right place it was needed... The paper was circulated to members of the RNA Tie Club but was never published in a proper journal. It is my most influential unpublished paper. Eventually I did publish a short remark briefly outlining the idea and tentatively suggesting that the adaptor might be a small piece of nucleic acid... As every molecular biologist now knows, the job is done by a family of molecules now called transfer RNA."

Crick, 'What Mad Pursuit' (1988), 95-6.

In 1958, Crick made two proposals: the sequence hypothesis and the central dogma. Both ideas are accepted today as central tenets of molecular biology. The sequence hypothesis was "that specificity of a piece of nucleic acid is expressed solely by the sequence of its bases, and this sequence is a (simple) code for the amino acid sequence of a particular protein."

The transfer of information from nucleic acid to proteins is, Crick proposed, a one-way street. This proposal the central dogma - states that "once information has passed into protein, it cannot get out again. In more detail, the transfer of information from nucleic cid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible."

Further reading

Crick F H C (1958) On protein synthesis. Symp. Soc. Exp. Biol. 12: 138-163

Crick FHC. On degenerate templates and adaptor hypothesis. Draft, [PDF]. Early 1955

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'The Crick papers: 1955 From DNA to protein' by Giles Newton
 
   
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