Agl24 is an ancient archaeal homolog of the eukaryotic N-glycan chitobiose synthesis enzymes

Benjamin H. Meyer (Lead / Corresponding author), Panagiotis S. Adam, Ben Wagstaff, George E. Kolyfetis, Alexander J. Probst, Sonja Verena Albers, Helge Dorfmueller (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
103 Downloads (Pure)

Abstract

Protein N-glycosylation is a post-translational modification found in organisms of all domains of life. The crenarchaeal N-glycosylation begins with the synthesis of a lipid-linked chitobiose core structure, identical to that in Eukaryotes, although the enzyme catalyzing this reaction remains unknown. Here, we report the identification of a thermostable archaeal β-1,4-N-acetylglucosaminyltransferase, named archaeal glycosylation enzyme 24 (Agl24), responsible for the synthesis of the N-glycan chitobiose core. Biochemical characterization confirmed its function as an inverting β-D-GlcNAc-(1→4)-α-D-GlcNAc-diphosphodolichol glycosyltransferase. Substitution of a conserved histidine residue, found also in the eukaryotic and bacterial homologs, demonstrated its functional importance for Agl24. Furthermore, bioinformatics and structural modeling revealed similarities of Agl24 to the eukaryotic Alg14/13 and a distant relation to the bacterial MurG, which are catalyzing the same or a similar reaction, respectively. Phylogenetic analysis of Alg14/13 homologs indicates that they are ancient in Eukaryotes, either as a lateral transfer or inherited through eukaryogenesis.

Original languageEnglish
Article numbere67448
Number of pages27
JournaleLife
Volume11
DOIs
Publication statusPublished - 8 Apr 2022

Keywords

  • Agl24
  • Alg13
  • Alg14
  • E. coli
  • N-glycosylation
  • Sulfolobus acidocladarius
  • biochemistry
  • chemical biology
  • chitobiose
  • infectious disease
  • microbiology

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology

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