CMT 1B: Transmembrane Domain of Myelin Protein Zero Can Form Dimers: Possible Im

[Guest guest]

Biochemistry. 2007 Oct 4

Transmembrane Domain of Myelin Protein Zero Can Form Dimers:

Possible Implications for Myelin Construction.

Plotkowski ML, Kim S, ML, Partridge AW, Deber CM, Bowie JU.

Department of Chemistry and Biochemistry, Molecular Biology

Institute, and University of California at Los Angeles-U.S.

Department of Energy Institute for Genomics and Proteomics,

University of California, Los Angeles, 611 E. Young Drive

East, Los Angeles, California 90095-1570, Department of Life

Science, POSTECH, Pohang, Kyungbuk 790-784, Korea, Division of

Molecular Structure and Function, Research Institute, Hospital for

Sick Children, Toronto M5G 1X8, Ontario, Canada, and Department of

Biochemistry, University of Toronto, Toronto M5S 1A8, Ontario,

Canada.

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 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.