Studies in structural neurobiology: Expression and purification of myelin protein zero and structural analysis of amyloid beta peptides

Myelin protein zero (P0) is an adhesion protein of peripheral nervous system myelin, and required for the formation and maintenance of myelin structure. Mutations and deletions in the P0 gene result in hereditary peripheral neuropathies of varying severity. Knowing the crystal structures of native and altered human P0 isoforms would elucidate the structural changes causing altered functionality. Here, we describe the expression and purification of human P0 extracellular domain suitable for crystallographic studies.; Amyloid-beta (Abeta) is the major amino acid peptide of neuritic plaques found in Alzheimer's disease. Various peptides containing residues 25 to 35 (Abeta(25--35)) were investigated with x-ray diffraction and electron microscopy. Diffraction patterns from Abeta(31--35) and Abeta(Phe31)(31--35) gave sharp reflections to 2.8 A Bragg spacing. Both peptides showed a reverse beta-turn at Gly33-Leu34, and side chain locations were determined. These results may elucidate Abeta folding pathways, and ultimately allow rational drug design to attenuate plaque formation.