Methionine in Proteins: It’s Not Just for Protein Initiation Anymore

Abstract

Methionine in proteins is often thought to be a generic hydrophobic residue, functionally replaceable with another hydrophobic residue such as valine or leucine. This is not the case, and the reason is that methionine contains sulfur that confers special properties on methionine. The sulfur can be oxidized, converting methionine to methionine sulfoxide, and ubiquitous methionine sulfoxide reductases can reduce the sulfoxide back to methionine. This redox cycle enables methionine residues to provide a catalytically efficient antioxidant defense by reacting with oxidizing species. The cycle also constitutes a reversible post-translational covalent modification analogous to phosphorylation. As with phosphorylation, enzymatically-mediated oxidation and reduction of specific methionine residues functions as a regulatory process in the cell. Methionine residues also form bonds with aromatic residues that contribute significantly to protein stability. Given these important functions, alteration of the methionine-methionine sulfoxide balance in proteins has been correlated with disease processes, including cardiovascular and neurodegenerative diseases. Methionine isn't just for protein initiation.

Methionine in proteins: The Cinderella of the proteinogenic amino acids

“…Hence, in the remainder we will present only a few examples that together outline the evolutionary potential of methionine sulfoxidation as a regulatory strategy. A more extensive review can be found at Reference .…”

Distinctive structural properties of THB11, a pentacoordinate Chlamydomonas reinhardtii truncated hemoglobin with N- and C-terminal extensions

“…It is tempting to speculate that the Met clustering could play a particular role for the regulation of ligand access in THB11, especially in the context of an algal host that photosynthetically produces reactive oxygen species on a regular basis. Met residues are prone to oxidation, a process that is reversible by methionine sulfoxide reductases and employed for antioxidative defense as well as for protein activity regulation [81]. We do not know where the THB11 C terminus would be located and if it would shield the ST access site, respectively.…”

Hypochlorite-induced oxidative modification of fibrinogen

“…Авторы работ [1,2] окислении может быть обусловлена окислением остатка метионина, АαMet476, нарушающего способность αC-областей окисленных молекул участвовать в латеральной агрегации протофибрилл. В этой связи следует отметить, что предпочтительное окисление АαMet476 по сравнению с другими многочисленными остатками метионинов в Аα-цепи свидетельствует о том, что этот остаток, по всей видимости, локализован на поверхности белка и может окисляться без существенных потерь в функциональной активности белка [15]. Кроме того, выявленные окислительные модификации других остатков, локализованных на αС-доменах и αC-коннекторах, также, вероятно, могут способствовать ослаблению взаимодействия αC-αC.…”