Methionine in proteins: The Cinderella of the proteinogenic amino acids

Abstract

Methionine in proteins, apart from its role in the initiation of translation, is assumed to play a simple structural role in the hydrophobic core, in a similar way to other hydrophobic amino acids such as leucine, isoleucine, and valine. However, research from a number of laboratories supports the concept that methionine serves as an important cellular antioxidant, stabilizes the structure of proteins, participates in the sequence‐independent recognition of protein surfaces, and can act as a regulatory switch through reversible oxidation and reduction. Despite all these evidences, the role of methionine in protein structure and function is largely overlooked by most biochemists. Thus, the main aim of the current article is not so much to carry out an exhaustive review of the many and diverse processes in which methionine residues are involved, but to review some illustrative examples that may help the nonspecialized reader to form a richer and more precise insight regarding the role‐played by methionine residues in such processes.

Impact of Early Pandemic Stage Mutations on Molecular Dynamics of SARS-CoV-2 Mpro

“…Even though both residues are hydrophobic, an increase in backbone motion was observed. It is possible that by the replacing of the unbranched methionine side chain 111 by the branched amino acid isoleucine, the potential for local mobility is reduced, possibly leading to far-ranging compensatory effects.…”

MICAL2 acts through Arp3B isoform-specific Arp2/3 complexes to destabilize branched actin networks

“…Given this, we wondered whether the Arp3Bdependent actin tail phenotype depends on oxidation of Met293. To investigate this possibility, we replaced Thr293 in Arp3 and Met293 in Arp3B with glutamine to mimic the Met-SO state (27,28). In both cases, the glutamine mutants induced the formation of shorter actin tails (Fig 4A, S4A).…”

Modifying Methionine on Proteins

“…Methionine is an essential and unique amino acid that plays a critical role in starting the protein‐synthesis process. It is also involved in the production of other sulfur‐containing molecules with important functions for the cells, such as glutathione, taurine, creatine, and perhaps most importantly, the methionine‐derived sulfonium cation S ‐adenosyl methionine (SAM), which alters DNA and RNA by adding a methyl group . In proteins methionine usually exists at a relatively low level (2 %) compared with other common amino acids; this offers the possibility of controllable functionalization at a specific location.…”