Crystal Structure of the Extracellular Domain from P 0, the Major Structural Protein of Peripheral Nerve Myelin

Abstract

P 0, the major protein of peripheral nerve myelin, mediates membrane adhesion in the spiral wraps of the myelin sheath. We have determined the crystal structure of the extracellular domain from P 0 (P 0ex) at 1.9 Å resolution. P 0ex is folded like a typical immunoglobulin variable-like domain; five residues at the C-terminus are disordered, suggesting a flexible linkage to the membrane. The requirements for crystallization of P 0ex are similar to those for maintaining the native extracellular spacing of adjacent myelin lamellae; thus, given the self-adhesive character of P 0ex, the crystal itself may reveal some of the natural interactions that occur between P 0 molecules in myelin. The structure leads to the suggestion that P 0 extracellular domains may emanate from the membrane surface as tetramers that link to tetramers on the opposing membrane surface, to result in the formation of networks of molecules. We report analytical ultracentrifugation data for P 0ex that support this idea.