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

preprint
revised on 04.10.2019 and posted on 07.10.2019 by Pablo Ricardo Arantes, Conrado Pedebos, Marcelo D. Poleto, Laércio Pol-Fachin, Hugo Verli

Lipid-linked oligosaccharides (LLOs) plays an important role in the N-glycosylation pathway as the donor substrate of oligosaccharyltransferases (OSTs), which are respon- sible 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 unde- caprenol in prokarya, whereas the number of isoprene units may change between species. Given the potential relevance of LLOs and their related enzymes to diverse biotechno- logical 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, 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) LLO 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. Dynamics of isoprenoid chains embedded within the bilayer are described and membrane dynamics and its related properties are also investigated. Overall, there are similarities regarding the structural and dynamics of the eukaryotic, the bacterial and the archaeal LLOs in bilayers, which can support the comprehension of their association with OSTs. This data may support future studies on the transferring mechanism of the oligosaccharide chain to an acceptor protein.

Funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq), MCT, Brasilia, DF, Brazil; the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) - CAPES/Drug Discovery grant number 23038.007777/2014-87, MEC, Brasilia, DF, Brazil.

The authors acknowledge the National Laboratory for Scientific Computing (LNCC/MCTI, Brazil) for providing HPC resources of the SDumont supercom- puter, which have contributed to the research results reported within this paper. URL: http://sdumont.lncc.br

History

Email Address of Submitting Author

pablitoarantes@gmail.com

Institution

Universiade Federal de Ciências da Saúde de Porto Alegre

Country

Brazil

ORCID For Submitting Author

0000-0003-1946-2750

Declaration of Conflict of Interest

The authors confirm that there is no conflict of interest to declare.

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