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Methionine



Methionine has a snake side chain. Or shall we call it a sneak? This linear non-branched hydrophobic side-chain can easily sneak into hydrophobic pockets of different shapes. Therefore, if you want to accommodate a hydrophobic substrate with a tricky shape, youd probably take methionine.

A methionine rich domain in signal-recognition particle (SRP) complex is the one responsible for recognition of hydrophobic sequences (i.e. the signal) emerging from the ribosome. Thus, it is essential for the SRP-mediated targeting to the translocon.

Although, methionine is an excellent hydrophobic amino acid, it has what the call in IT a critical vulnerability: it is prone to oxidation. When sulfur is oxidized by reactive oxygen species, this creates first a sulfoxide and then sulfone. Both are polar. Therefore, oxidation of methionine is a detrimental process for proteins having methionine side chain in the hydrophobic core. Reversal of the methionine oxidation is a serious task undertaken by methionine sulfoxide reductases. If these enzymes forget to reduce the side-chain when its still a sulfoxide, beware, next oxidation will make a sulfone, and the transition will be settled irreversible.

Interestingly, participation in translation is not the main role of methionine in living cells. The main function of this amino acid is formation of S-adenosyl-methionine (known as SAM or AdoMet). This key metabolite is involved in a variety of processes: radical chemistry, C1-metabolism, methylation reactions (e.g. DNA methylation) and polyamine biosynthesis.

Somehow mysterious is the fact that every protein sequence starts with a methionine (N-formyl methionine in bacteria), i.e. methionine codon AUG is also the start codon. The reason for this is still unknown, though.

Interesting readings:

- Wild, K., et al. SRP meets the ribosome. Nat. Struct. Mol. Biol., 11, 2004, 1049-1053, doi: 10.1038/nsmb853

The structural model of SRP-mediated ribosome-nascent chain complex targeting to the translocon. The first and key step is the interaction of the C-terminal methionine-rich domain with the N-terminal hydrophobic protein stretch emerging from the ribosome.

- Moskovitz, J. Methionine sulfoxide reductases: ubiquitous enzymes involved in antioxidant defense, protein regulation, and prevention of aging-associated diseases. Biochim. Biophys. Acta,, 1703, 2005, 213-219, doi: 10.1016/j.bbapap.2004.09.003

A review of the methionine sulfoxide reductases, important cellular antioxydants.

- Laurino, P. and Tawfik, D. S. Spontaneous Emergence of S-Adenosylmethionine and the Evolution of Methylation. Angew. Chem. Int. Ed., 56, 2017, 343-345, doi: 10.1002/anie.201609615

Prebiotic chemistry. The paper demonstrates spontaneous emergence of SAM, an important cellular metabolite, and describes conditions for this process.