Cytoplasmic domain of human myelin protein zero likely folded as β-structure in compact myelin

XiaoYang Luo, Deepak Sharma, Hideyo Inouye, Daniel Lee, Robin L. Avila, Mario Salmona, Daniel A. Kirschner

Research output: Contribution to journalArticle

Abstract

Myelin protein zero (P0 or P0 glycoprotein), the major integral membrane protein in peripheral nervous system myelin, plays a key role in myelin membrane compaction and stability. While the structure of P0 extracellular domain was determined by crystallography, the paucity of any structural data on the highly positive-charged P0 cytoplasmic domain (P0-cyt) has greatly limited our understanding of the mechanism of P0 function. Here, using circular dichroism and intrinsic fluorescence spectroscopy, we attempted to elucidate the structure of human P0-cyt (hP0-cyt) in membrane mimetic environments composed of detergents or lipid vesicles. We found that the secondary structure of P0-cyt was polymorphic - at the lipid/protein ratio corresponding to that of mature peripheral myelin (∼50:1), hP0-cyt mainly adopted a β-conformation, whereas when the proportion of lipid increased, the structure underwent a β→α transition. By contrast, the secondary structure of the major isoform of myelin basic protein, another myelin protein with a very large positive charge, remained unchanged across a wide range of lipid/protein ratios. We propose that when hP0-cyt is bound at sufficient concentration to lamellar lipid bilayers such as myelin, it folds into a β-conformation; before this threshold lipid/protein ratio is reached, the domain is α-helical. We suggest that the cytoplasmic apposition (major dense line) in compact myelin may be stabilized via the hydrogen-bonding of β-strands formed as a result of local P0-P0 aggregation.

Original languageEnglish
Pages (from-to)1585-1597
Number of pages13
JournalBiophysical Journal
Volume92
Issue number5
DOIs
Publication statusPublished - Mar 2007

ASJC Scopus subject areas

  • Biophysics

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