Lipid-linked oligosaccharides in membranes sample conformations that facilitate binding to oligosaccharyltransferase.

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TitleLipid-linked oligosaccharides in membranes sample conformations that facilitate binding to oligosaccharyltransferase.
Publication TypeJournal Article
Year of Publication2014
AuthorsKern, NR, Lee, HSun, Wu, EL, Park, S, Vanommeslaeghe, K, Mackerell, AD, Klauda, JB, Jo, S, Im, W
JournalBiophys J
Volume107
Issue8
Pagination1885-95
Date Published2014 Oct 21
ISSN1542-0086
KeywordsAmino Acid Sequence, Bacterial Proteins, Carbohydrate Conformation, Carbohydrate Sequence, Hexosyltransferases, Lipid Bilayers, Lipopolysaccharides, Membrane Proteins, Molecular Dynamics Simulation, Molecular Sequence Data, Protein Binding
Abstract

Lipid-linked oligosaccharides (LLOs) are the substrates of oligosaccharyltransferase (OST), the enzyme that catalyzes the en bloc transfer of the oligosaccharide onto the acceptor asparagine of nascent proteins during the process of N-glycosylation. To explore LLOs' preferred location, orientation, structure, and dynamics in membrane bilayers of three different lipid types (dilauroylphosphatidylcholine, dimyristoylphosphatidylcholine, and dioleoylphosphatidylcholine), we have modeled and simulated both eukaryotic (Glc3-Man9-GlcNAc2-PP-Dolichol) and bacterial (Glc1-GalNAc5-Bac1-PP-Undecaprenol) LLOs, which are composed of an isoprenoid moiety and an oligosaccharide, linked by pyrophosphate. The simulations show no strong impact of different bilayer hydrophobic thicknesses on the overall orientation, structure, and dynamics of the isoprenoid moiety and the oligosaccharide. The pyrophosphate group stays in the bilayer head group region. The isoprenoid moiety shows high flexibility inside the bilayer hydrophobic core, suggesting its potential role as a tentacle to search for OST. The oligosaccharide conformation and dynamics are similar to those in solution, but there are preferred interactions between the oligosaccharide and the bilayer interface, which leads to LLO sugar orientations parallel to the bilayer surface. Molecular docking of the bacterial LLO to a bacterial OST suggests that such orientations can enhance binding of LLOs to OST.

DOI10.1016/j.bpj.2014.09.007
Alternate JournalBiophys. J.
PubMed ID25418169
PubMed Central IDPMC4213670
Grant ListR01 GM072558 / GM / NIGMS NIH HHS / United States
R01 GM070855 / GM / NIGMS NIH HHS / United States
P20 GM103418 / GM / NIGMS NIH HHS / United States
GM070855 / GM / NIGMS NIH HHS / United States
GM072558 / GM / NIGMS NIH HHS / United States