Deciphering the conformational dynamics of Myelin Oligodendrocyte glycoprotein in the myelin sheath

Abstract

Myelin Oligodendrocyte Glycoprotein (MOG) is a transmembrane protein in the myelin sheath. It acts as an auto-antigen under certain unknown conditions causing demyelination, thus resulting in Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease (MOGAD). The significance of glycosylation in the conformational dynamics of the extracellular region (EC1) of the MOG were evident from the previous computational studies. Here, in this study, we performed the molecular dynamics simulation of the entire human MOG in the myelin sheath for 100 ns using the NAMD program. The results indicated that the EC1 and cytoplasmic region (CP) dominate the conformational rigidity of the protein, and enhance its interaction with lipids. This in turn helps in maintaining the myelin integrity in the presence of glycan. The transmembrane regions have reduced interaction with lipids in the glycosylated system. Moreover, the C-terminal extracellular region 2 (EC2) behaves exactly opposite to that of EC1 in the glycan presence. This may be attributed to the glycosylation site in the EC1 region. Hence, not only the region EC1 (having 3 crucial epitopes) but even the CP region were important for understanding the proper function of MOG in the glycan presence.

Communicated by Ramaswamy H. Sarma

Keywords:

• MOG
• myelin sheath
• AMBER
• glycam
• MOGAD

Acknowledgements

The authors acknowledge the support from SASTRA Deemed to be University for providing the necessary computational facilities.

Author’s contributions

LR: Conceptualization, resources, methodology, data curation, analysis, interpretation, figures designed, writing – original, revision.

AYK: analyzed the data and figures prepared.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.