Copper uptake induces self-assembly of 18.5 kDa myelin basic protein (MBP).

Myelin basic protein (MBP) is predominantly found in the membranes of the myelin sheath of the central nervous system and is involved in important protein-protein and protein-lipid interactions in vivo and in vitro. Furthermore, divalent transition metal ions, especially Zn(2+) and Cu(2+), seem to directly affect the MBP-mediated formation and stabilization of the myelin sheath of the central nervous system. MBP belongs to the realm of intrinsically disordered proteins, and only fragmentary information is available regarding its partial structure(s) or supramolecular arrangements. Here, using standard continuous wave and modern pulse electron paramagnetic resonance methods, as well as dynamic light scattering, we demonstrate the uptake and specific coordination of two Cu(2+) atoms or one Zn(2+) atom per MBP molecule in solution. In the presence of phosphates, further addition of divalent metal ions above a characteristic threshold of four Cu(2+) atoms or two Zn(2+) atoms per MBP molecule leads to the formation of large MBP aggregates within the protein solution. In vivo, MBP-MBP interactions may thus be mediated by divalent cations.