An Immunodominant Epitope of Myelin Basic Protein Is an Amphipathic α-Helix

• Published in: The Journal of biological chemistry Vol. 279; no. 7; p. 5757
• Main Authors: Ian R. Bates, Jimmy B. Feix, Joan M. Boggs, George Harauz
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 13-02-2004
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M311504200

Myelin basic protein is a candidate autoantigen in multiple sclerosis. One of its dominant antigenic epitopes is segment Pro 85 to Pro 96 (human sequence numbering, corresponding to Pro 82 to Pro 93 in the mouse). There have been several, contradictory predictions of secondary structure in this region; either β-sheet,
α-helix, random coil, or combinations thereof have all been proposed. In this paper, molecular dynamics and site-directed
spin labeling in aqueous solution indicate that this segment forms a transient α-helix, which is stabilized in 30% trifluoroethanol.
When bound to a myelin-like membrane surface, this antigenic segment exhibits a depth profile that is characteristic of an
amphipathic α-helix, penetrating up to 12 Å into the bilayer. The α-helix is tilted ∼9°, and the central lysine is in an ideal
snorkeling position for side-chain interaction with the negatively charged phospholipid head groups.