Lipid membrane association of myelin proteins and peptide segments studied by oriented and synchrotron radiation circular dichroism spectroscopy.
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.
Centre for Structural Systems Biology, Helmholtz Centre for Infection Research (CSSB-HZI) , German Electron Synchrotron (DESY), Hamburg 22607, Germany.
Gopinath
G
Muruganandam
Jochen
J
Bürck
Anne S
AS
Ulrich
Inari
I
Kursula
Petri
P
Kursula
D002942:Circular Dichroism; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D009185:Myelin Proteins / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D017356:Synchrotrons
D008051:Lipid Bilayers; D009185:Myelin Proteins; D010455:Peptides