The Lazy Life of Lipid-Linked Oligosaccharides in All Life Domains

Lipid-linked oligosaccharides (LLOs) play an important role in the N-glycosylation pathway as the donor substrate of oligosaccharyl­transferases (OSTs), which are responsible for the en bloc transfer of glycan chains onto a nascent polypeptide. The lipid component of LLO in both eukarya and archaea...

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Published inJournal of chemical information and modeling Vol. 60; no. 2; pp. 631 - 643
Main Authors Arantes, Pablo R, Pedebos, Conrado, Polêto, Marcelo D, Pol-Fachin, Laércio, Verli, Hugo
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 24.02.2020
Subjects
Archaea
Carbohydrate Conformation
Cell Membrane - metabolism
Chains
Complex formation
Computer simulation
Domains
Dynamic structural analysis
Glycan
Glycosylation
Isoprene
Lipid Metabolism
Lipids
Membranes
Models, Molecular
Molecular dynamics
Oligosaccharides
Oligosaccharides - chemistry
Oligosaccharides - metabolism
Polypeptides
Proteins
Quantum mechanics
Substrates
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Summary:Lipid-linked oligosaccharides (LLOs) play an important role in the N-glycosylation pathway as the donor substrate of oligosaccharyl­transferases (OSTs), which are responsible for the en bloc transfer of glycan chains onto a nascent polypeptide. The lipid component of LLO in both eukarya and archaea consists of a dolichol, and an undecaprenol in prokarya, whereas the number of isoprene units may change between species. Given the potential relevance of LLOs and their related enzymes to diverse biotechnological applications, obtaining reliable LLO models from distinct domains of life could support further studies on complex formation and their processing by OSTs, as well as protein engineering on such systems. In this work, molecular modeling techniques, such as quantum mechanics calculations, molecular dynamics simulations, and metadynamics were employed to study eukaryotic (Glc3-Man9-GlcNAc2-PP-Dolichol), bacterial (Glc1-GalNAc5-Bac1-PP-Undecaprenol), and archaeal (Glc1-Man1-Gal1-Man1-Glc1-Gal1-Glc1-P-Dolichol) LLOs in membrane bilayers. Microsecond molecular dynamics simulations and metadynamics calculations of LLOs revealed that glycan chains are more prone to interact with the membrane lipid head groups, while the PP linkages are positioned at the lipid phosphate head groups level. The dynamics of isoprenoid chains embedded within the bilayer are described, and membrane dynamics and related properties are also investigated. Overall, there are similarities regarding the structure and dynamics of the eukaryotic, the bacterial, and the archaeal LLOs in bilayers, which can support the comprehension of their association with OSTs. These data may support future studies on the transferring mechanism of the oligosaccharide chain to an acceptor protein.
ISSN:1549-9596
1549-960X
DOI:10.1021/acs.jcim.9b00904