Recombinant Human ALG1L Protein

ALG1L (Asparagine-Linked Glycosylation 1 Homolog-Like), a human homolog of the yeast ALG1 gene, encodes a conserved mannosyltransferase critical in the early steps of N-linked glycoprotein biosynthesis. Functioning predominantly in the endoplasmic reticulum, ALG1L catalyzes the transfer of mannose from dolichol-linked mannose (Dol-P-Man) to lipid-linked oligosaccharides (LLOs), forming the Man5GlcNAc2-PP-dolichol intermediate—a precursor essential for subsequent glycan assembly. Structural studies reveal that ALG1L adopts a GT-B fold topology, common to glycosyltransferases, with distinct α-helical and β-sheet domains facilitating substrate binding and catalysis. Unlike its paralog ALG1. ALG1L lacks transmembrane domains but associates with membranes through protein-protein interactions, potentially forming complexes with other ALG family members (e.g., ALG2) to enhance reaction efficiency.

Recombinant ALG1L expression systems (e.g., E. coli, insect cells) have enabled detailed biochemical characterization, including its dependence on Mn²⁺/Mg²⁺ cofactors and pH optima (~7.5). Mutations in ALG1L orthologs are linked to congenital disorders of glycosylation (CDG), neurodevelopmental defects, and impaired immunity in model organisms, highlighting its biological necessity. Recent studies implicate ALG1L dysregulation in cancers, where altered glycosylation patterns influence tumor cell adhesion, metastasis, and drug resistance. Its recombinant form is also leveraged to study substrate specificity and inhibitor screening for therapeutic development. Despite functional overlap with ALG1. ALG1L exhibits distinct tissue-specific expression profiles, suggesting specialized roles in mammalian systems. Further research aims to clarify its regulatory mechanisms and potential as a biomarker or therapeutic target.