Lipid Membrane
Association of Myelin Proteins and
Peptide Segments Studied by Oriented and Synchrotron Radiation Circular
Dichroism Spectroscopy
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Abstract
Myelin-specific
proteins are either integral or peripheral membrane
proteins that, in complex with lipids, constitute a multilayered proteolipid
membrane system, the myelin sheath. The myelin sheath surrounds the
axons of nerves and enables rapid conduction of axonal impulses. Myelin
proteins interact intimately with the lipid bilayer and play crucial
roles in the assembly, function, and stability of the myelin sheath.
Although myelin proteins have been investigated for decades, their
structural properties upon membrane surface binding are still largely
unknown. In this study, we have used simplified model systems consisting
of synthetic peptides and membrane mimics, such as detergent micelles
and/or lipid vesicles, to probe the conformation of peptides using
synchrotron radiation circular dichroism spectroscopy (SRCD). Additionally,
oriented circular dichroism spectroscopy (OCD) was employed to examine
the orientation of myelin peptides in macroscopically aligned lipid
bilayers. Various representative peptides from the myelin basic protein
(MBP), P0, myelin/oligodencrocyte glycoprotein, and connexin32 (cx32)
were studied. A helical peptide from the central immunodominant epitope
of MBP showed a highly tilted orientation with respect to the membrane
surface, whereas the N-terminal cytoplasmic segment of cx32 folded
into a helical structure that was only slightly tilted. The folding
of full-length myelin basic protein was, furthermore, studied in a
bicelle environment. Our results provide information on the conformation
and membrane alignment of important membrane-binding peptides in a
membrane-mimicking environment, giving novel insights into the mechanisms
of membrane binding and stacking by myelin proteins