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Paul C. Anagnostopoulos
31st January 2007, 06:35 AM
Anfinsen's principle states that the three-dimensional folding of a protein is based solely on its amino acid sequence. It appears that yet another cell biology principle is oversimplified.

In the latest issue of Science, an article describes the discovery of proteins with the same amino acid sequence but variant functions. How can this be?

A single-point mutation that still codes for the same amino acid is called a silent single nucleotide polymorphism (SNP). It is "silent" because it has no affect on the final protein, and thus, according to Anfinsen, no affect on the protein's structure. However, it turns out that it can have an affect on the rate at which amino acids are added to the nascent protein by the ribosome. This is because some aminoacyl-transfer RNAs* are more common than others, and the ribosome works more quickly when the tRNAs are plentiful. The speed at which amino acids are added can have an affect on the folding of the protein, and so its final structure, and so its function.

Beware the simplistic cell biology principle!

~~ Paul

* An aminoacyl-transfer RNA (tRNA) is a molecule that matches a codon triplet at one end and carries an amino acid at the other. These deliver amino acids to the ribosome and match up with the messenger RNA that codes the gene.

sphenisc
31st January 2007, 07:18 AM
...
In the latest issue of Science, an article describes the discovery of proteins with the same amino acid sequence but variant functions.
...



http://www.sciencemag.org/cgi/content/short/315/5811/525

Paul C. Anagnostopoulos
31st January 2007, 07:28 AM
Thanks, Sphensic!

~~ Paul

kleinman
31st January 2007, 09:33 AM
Anfinsen's principle states that the three-dimensional folding of a protein is based solely on its amino acid sequence. It appears that yet another cell biology principle is oversimplified.

In the latest issue of Science, an article describes the discovery of proteins with the same amino acid sequence but variant functions. How can this be?
There are many variables that affect the three-dimensional folding of a protein (and other biological molecules as well). Start with temperature. DNA can be made to denature by heating this molecule. The electro-chemical environment in which the protein resides affects its configuration. For example, changing the polarity of the solution will affect its configuration since some amino acids are polar and others non-polar. pH affects proteins, concentrations of different solutes will change the electro-chemical environment in which a protein resides and on and on for the myriad of variables which affect the configuration which a protein can take.

Trying2Bopen
31st January 2007, 11:32 AM
This is fascinating!



There are many variables that affect the three-dimensional folding of a protein (and other biological molecules as well). Start with temperature. DNA can be made to denature by heating this molecule. The electro-chemical environment in which the protein resides affects its configuration. For example, changing the polarity of the solution will affect its configuration since some amino acids are polar and others non-polar. pH affects proteins, concentrations of different solutes will change the electro-chemical environment in which a protein resides and on and on for the myriad of variables which affect the configuration which a protein can take.


Yes, but what makes this special is that we are talking about two proteins of the same sequence in the same environment that have different functions based on the availability of tRNA. This is just absolutely fascinating and completely beautiful.

sphenisc
1st February 2007, 03:49 AM
Full article here:

http://www.inmegen.gob.mx/mambo/images/stories/ensenanza/club/2007/jci-240107.pdf

DeviousB
1st February 2007, 04:01 AM
What impact will this have on neutral molecular evolution? If some (perhaps many) SNPs are not as silent as previously thought will we have to recalibrate some of the 'molecular clocks' we use to date phylogenetic events?