Folding and function of the myelin proteins from primary sequence data.

Area of Science:

• * Molecular biology and bioinformatics
• * Neurochemistry and structural biology

Background:

• * Understanding myelin protein structure is crucial for myelin sheath organization and function.
• * Except for PNS myelin P2 basic protein, most myelin protein structures remain unknown.

Purpose of the Study:

• * To predict molecular folding and functions of myelin proteins using primary sequence data.
• * To analyze secondary structure propensities and physical-chemical parameters of myelin proteins.

Main Methods:

• * Developed a FORTRAN program for protein primary sequence analysis.
• * Calculated average values, autocorrelation functions, and Fourier transforms of sequence parameters.
• * Aligned protein sequences and plotted correlation coefficients to identify homologies.

Main Results:

• * Conserved residues in rodent and shark myelin basic protein (MBP) and P0 glycoprotein (P0) align with predicted alpha/beta conformations.
• * P0 glycoprotein's extracellular domain shows immunoglobulin-like beta propensity; cytoplasmic domain exhibits alpha-beta-alpha folding.
• * Identified potential functional motifs including N-glycosylation, phosphorylation, and nucleotide binding sites in myelin proteins.

Conclusions:

• * Proposed that P0 glycoprotein's beta-sheets orient parallel to the membrane for extracellular interaction.
• * An extra beta-fold in shark P0 may enhance extracellular surface attraction, explaining smaller extracellular space.
• * Nucleotide binding sites in PLP, MBP, and CNP correlate with observed experimental functions.