Omannosyl

Omannosyl, or O-mannosylation, refers to a type of protein glycosylation in which a mannose sugar is attached to the hydroxyl group of serine or threonine residues. It is a form of O-linked glycosylation found in many eukaryotes, including animals and fungi, and contributes to protein folding, stability, and interactions with the extracellular matrix.

Biochemical pathway and structure: In metazoans, O-mannosylation begins in the endoplasmic reticulum with the transfer of a mannose from dolichol-phosphate-mannose to Ser or Thr residues, mediated by protein O-mannosyltransferases such as POMT1 and POMT2. In the Golgi apparatus, additional glycosyltransferases elaborates the initial mannose into more complex O-mannosyl glycans. A notable example is the matriglycan on alpha-dystroglycan, an extended structure that enables binding to laminin and other extracellular matrix components, supporting basement membrane integrity.

Biological significance: Proper O-mannosylation is essential for the function of several extracellular matrix receptors and is implicated in muscle and nervous system development. Defects in O-mannosylation pathways can lead to dystroglycanopathies, a group of congenital muscular dystrophies with brain involvement, including conditions such as Walker-Warburg syndrome and muscle–eye–brain disease.

Evolution and scope: O-mannosylation occurs across diverse eukaryotes, including fungi, where it contributes to cell wall glycoprotein architecture. The specific enzymes and final glycan structures vary among lineages, but the core concept remains the attachment of mannose to Ser/Thr residues.

Terminology: The term can describe either the modification itself or the glycoproteins bearing it; in literature the process is commonly called O-mannosylation, with the attached sugar referred to as the O-mannose residue.