Virtual Molecule: P0 Myelin Glycoprotein. I. Homology Modeling and Prediction of the Secondary and Tertiary Structure - Molecules: Nucleation, Aggregation and Crystallization - page 237

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Virtual Molecule:
P0 Myelin Glycoprotein.
I. Homology Modeling and Prediction
of the Secondary and Tertiary
Structure
Jan Pawel Jastrzebski* ,† and Jan Sedzik ‡
The P0 protein is a structural glycoprotein that accounts for more than 50% of the
peripheral nervous system myelin membrane protein and is associated with human
Charcot-Marie-Tooth disease. The P0 glycoprotein consists of three parts: the
extracellular domain, the single helix transmembrane region, and the intracellular
domain. The three-dimensional atomic structure of the full sequence P0 glyprotein
has not yet been solved. Using homology modeling with secondary and tertiary
structure prediction, it is possible to construct in silico a three-dimensional model
of this protein embedded in the lipid bilayer. Further detailed analyses of such a
model allow one to distinguish theoretical autoimmune epitopes and to visualize
molecular effects and chemical changes in the molecule. For example, breaking a
disulfide bridge can cause the opening of the P0_Ex part of the protein, leading to
a decrease in migration speed of the “opened” protein in the SDS-PAGE.
Keywords: Homology modeling; comparative modeling; structure prediction;
threading; myelin; P0; HNK-1; epitopes.
*Corresponding author.
† Department of Plant Physiology and Biotechnology, Faculty of Biology, University of
Warmia and Mazury, ul. Oczapowskiego 1A/113, 10-719 Olsztyn, Poland. E-mail: jan.
[e-mail].
‡ Karolinska Institutet, Protein Crystallization Facility, NOVUM, Stockholm, Sweden.
E-mail: [e-mail].