The Human Myelin Proteome and Sub-Metalloproteome Interaction Map: Relevance to Myelin-Related Neurological Diseases

Myelin in humans is composed of about 80% lipids and 20% protein. Initially, myelin protein composition was considered low, but various recent proteome analyses have identified additional myelin proteins. Although, the myelin proteome is qualitatively and quantitatively identified through complementary proteomic approaches, the corresponding Protein-Protein Interaction (PPI) network of myelin is not yet available. In the present work, the PPI network was constructed based on available experimentally supported protein interactions of myelin in PPI databases. The network comprised 2017 PPIs between 567 myelin proteins. Interestingly, structure-based in silico analysis revealed that 20% of the myelin proteins that are interconnected in the proposed PPI network are metal-binding proteins/enzymes that construct the main sub-PPI network of myelin proteome. Finally, the PPI networks of the myelin proteome and sub-metalloproteome were analyzed ontologically to identify the biochemical processes of the myelin proteins and the interconnectivity of myelin-associated diseases in the interactomes. The presented PPI dataset could provide a useful resource to the scientific community to further our understanding of human myelin biology and serve as a basis for future studies of myelin-related neurological diseases and particular autoimmune diseases such as multiple sclerosis where myelin epitopes are implicated.