Role of N-glycan in the structural changes of myelin oligodendrocyte glycoprotein and its complex with an antibody

Abstract

Myelin Oligodendrocyte Glycoprotein (MOG) is found on the external surface of the myelin sheath and plays an important role in neurodegenerative diseases. It was observed that the protein MOG acts as an autoantigen and results in demyelination. The cause for the sudden change of protein to be autoantigen is still unclear. Here we present the molecular dynamics simulation studies of MOG in both unbound and bound states with an antibody. Both these systems were studied in the absence and presence of N-glycan in order to understand the effect of glycosylation in the MOG conformational changes. The results indicate that the glycosylation decreases the flexibility of protein in both free and bound states. Glycan influence the interaction of the complex with the water molecules whereas free protein MOG interaction with water molecules was not affected by the glycosylation. Glycan changes the 3₁₀ helices adjacent to the antibody interacting epitope MOG_35-55 to turns.

Communicated by Ramaswamy H. Sarma

Keywords:

• Myelin oligodendrocyte glycoprotein
• fragment antibody
• N-acetylglucosamine
• AMBER
• GLYCAM

Acknowledgments

The author thanks them for the financial support and also acknowledges the support from SASTRA Deemed to be University for providing the necessary computational facilities. The author thanks the unknown reviewers for their important suggestions to improve the article.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the DST-Science and Engineering Research Board (SERB), Government of India (ECR/2017/000192).