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Biophys. J. BioFAST: First Published December 1, 2006. doi:10.1529/biophysj.106.094722
© 2006 by the Biophysical Society.

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MEMBRANES

CYTOPLASMIC DOMAIN OF HUMAN MYELIN P0 LIKELY FOLDED AS {beta} STRUCTURE IN COMPACT MYELIN

XiaoYang (Tony) Luo 1, Deepak Sharma 1, Hideyo Inouye 1, Daniel Lee 1, Robin L Avila 1, Mario Salmona 2 and Daniel A. Kirschner 3*

1 Boston College
2 Istituto di Ricerche Farmacologiche
3 Boston College - Higgins Hall

* To whom correspondence should be addressed. E-mail: kirschnd{at}bc.edu.

Submitted on August 3, 2006
Revised on September 11, 2006
Accepted on 3 November 2006


  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 (P0-ED) 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 {beta}-conformation whereas when the proportion of lipid increased, the structure underwent a {beta}->{alpha} transition. By contrast, the secondary structure of the major isoform of myelin basic protein (MBP), 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 {beta}-conformation; before this threshold lipid:protein ratio is reached, the domain is {alpha}-helical. We suggest that the cytoplasmic apposition (major dense line) in compact myelin may be stabilized via the hydrogen-bonding of {beta}-strands formed as a result of local P0-P0 aggregation.

Key Words: circular dichroism, intricsic fluorescence spectroscopy, lipid-protein vesicles, membrane adhesion, peripheral nervous system, small-angle x-ray diffraction




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X. Luo, H. Inouye, A. A. R. Gross, M. M. Hidalgo, D. Sharma, D. Lee, R. L. Avila, M. Salmona, and D. A. Kirschner
Cytoplasmic Domain of Zebrafish Myelin Protein Zero: Adhesive Role Depends on {beta}-Conformation
Biophys. J., November 15, 2007; 93(10): 3515 - 3528.
[Abstract] [Full Text] [PDF]


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Copyright © 2006 by the Biophysical Society.