Hello everyone,

 

I am having a hard time figuring this one out. I know that N-formylmethionine is the "start" amino acid during prokaryotic translation. But WHY does the methionine have to formylated? What is the point of formylating it, only for it to be deformylated, or completely cleaved, later during protein modifications? Thank you so much for reading my post! I greatly appreciate it.

Edited February 14, 201213 yr by jbpharm

Curious, is this something that could be described as an aid in the facilitation of future cleavage by reducing the bond potential, where defomylating would consolidate the bond?

Edited February 16, 201213 yr by Xittenn

Some additional facts:

• There is a specific tRNA for N-formyl-methionine.
• N-formyl-methionine (fMet) is only used in Bacteria and not in Archaea (which are also prokaryotes).
• Archaea also have Shine-Dalgarno sequences to initiate translation.
• Blocking the amino-group by a formyl group prevents the charged tRNA for N-formyl-methionine (tRNA_f) to be used in elongation of the protein.
• In fMet the N is in an amid bond like in a peptide. Just with the difference that no amino acid is used but formic acid. The positive charge of the NH₃ group has disappeared and instead you have a planar amid containing a CO group as H-bond receptor. So this is quite a dramatic change.
• fMet-tRNA_f initially binds to the P-site of the ribosome.

 

 

Speculation:

Since fMet closely resembles a peptide, you might assume that the Bacteria ribosome can only accept tRNAs with peptide-like ligands in the P-Site (which seems to be completely logical, since the P-site always binds the peptide, that's why it is called like this.). This feature could be an additional security feature to prevent translocation before the peptide bond is formed and thereby preventing the production of proteins which are cut into two pieces.

Archaea seem to have found a different solution to the problem.

 

So the formyl-group might be the analogous thing as the primer RNA for DNA synthesis.

Edited September 15, 201213 yr by Jens

Here the structures to better understand why N-formyl-Met has the same structure as a peptide:

 

....by the way: These kind of questions (pointing out an apparent paradox) are exactly the interesting ones. Discussing potential answers help to increase true understanding....

This all makes sense, but I am couriosu what is the analogous mechanism in eukaryotes then, I know eukaryotes also have two different Met-tRNAs, one for the START codon and the other for Methionine downstream of the START codon, how do they differ?

Years and years ago in grad school I heard the theory that f-met is used in prokaryotes which have polycistronic messages to prevent the accidental joining of the C-terminus of the previous polypeptide with the N-terminus of the next polypeptide coded for by the polycistronic message. Recently, I have not seen this theory espoused anywhere, so has it been disproven?