title: Transmembrane domain of myelin protein zero can form dimers: possible implications for myelin construction.
abstract: Myelin protein zero (MPZ) is the major integral membrane protein of peripheral nerve myelin in higher vertebrates, mediating homoadhesion of the multiple, spiraling wraps of the myelin sheath. Previous studies have shown that full-length MPZ can form dimers and tetramers, and biochemical studies on the extracellular domain (ECD) indicate that it can form a tetramer, albeit very weakly. On the basis of cross-linking studies and equilibrium sedimentation of a transmembrane (TM) domain peptide (MPZ-TM), we find that the MPZ-TM can form homodimers. We further characterized the dimer by measuring the effects of alanine and leucine substitutions on the ability of the TM to dimerize in Escherichia coli membranes. Our results indicate that the primary packing interface for the MPZ TM homodimer is a glycine zipper (GxxxGxxxG) motif. We also find that the G134R mutation, which lies within the glycine zipper packing interface and causes Charcot-Marie-Tooth disease type 1B, severely inhibits dimerization, suggesting that dimerization of the TM domain may be important for the normal functioning of MPZ. By combining our new results with prior work, we suggest a new model for an MPZ lattice that may form during the construction of myelin.
authors.affiliation: Department of Chemistry and Biochemistry, Molecular Biology Institute, and University of California at Los Angeles, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Plotkowski
authors.forename: Sanguk
authors.initials: S
authors.lastname: Kim
authors.forename: Martin L
authors.initials: ML
authors.lastname: Phillips
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Partridge
authors.forename: Charles M
authors.initials: CM
authors.lastname: Deber
authors.forename: James U
authors.initials: JU
authors.lastname: Bowie
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D002942:Circular Dichroism; D017931:DNA Primers; D019281:Dimerization; D016297:Mutagenesis, Site-Directed; D018993:Myelin P0 Protein / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D017931:DNA Primers; D018993:Myelin P0 Protein