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More MS news articles for November 2003

An immunodominant epitope of myelin basic protein is an amphipathic alpha-helix

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14630913&dopt=Abstract

Free Full Text at:
http://www.jbc.org/cgi/reprint/M311504200v1.pdf

J Biol Chem. 2003 Nov 20
Bates IR, Feix JB, Boggs JM, Harauz G.
Molecular Biology Genetics, University of Guelph, Guelph, Ontario N1G 2W1.

Myelin basic protein (MBP) is a candidate autoantigen in multiple sclerosis.

One of its dominant antigenic epitopes is segment Pro85 to Pro96 (human sequence numbering, corresponding to Pro82 to Pro93 in the mouse).

There have been several, contradictory predictions of secondary structure in this region; either beta-sheet, alpha-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 alpha-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 alpha-helix, penetrating up to 12 into the bilayer.

The alpha-helix is tilted ~9 degrees, and the central lysine is in an ideal snorkeling position for side chain interaction with the negatively charged phospholipid head groups.