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Predicted Folding of β‐Structure in Myelin Basic Protein
Author(s) -
Stoner Gerald L.
Publication year - 1984
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1984.tb00919.x
Subject(s) - circular dichroism , protein secondary structure , protein folding , protein structure , chemistry , folding (dsp implementation) , biophysics , peptide sequence , crystallography , turn (biochemistry) , helix (gastropod) , myelin basic protein , sequence (biology) , stereochemistry , biochemistry , myelin , biology , neuroscience , gene , electrical engineering , engineering , central nervous system , ecology , snail
Predictions of myelin basic protein secondary structure have not previously considered a major role for β‐structure in the organization of the native molecule because optical rotatory dispersion and circular dichroism studies have provided little, if any, evidence for β‐structure, and because a polycationic protein is generally considered to resist folding into a compact structure. However, the Chou‐Fasman, Lim, and Robson algorithms identify a total of five β‐strands in the amino acid sequence. Four of these hydrophobic amino acid sequences (37–45, 87–95, 110–118, and 150–158) could form a hairpin intermediate that initiates folding of a Greek‐key‐type β‐structure. A second fold on the more hydrophobic side, with the addition of a strand from the N‐terminus (residues 13–21), would complete the five‐stranded an‐tiparallel β‐sheet. A unique strand alignment can be predicted by phasing the hydrophobic residues. The unusual triproline sequence of myelin basic protein (100–102) is enclosed in the 14‐residue hairpin loop. If these prolines are in the trans conformation, models show that a reverse turn could occur at residues 102–105 (Pro‐Ser‐Gln‐Gly). Algorithms do not agree on the prediction of α‐helices, but each of the two large loops could accommodate an α‐helix. Myelin basic protein is known to be phosphor‐ylated in vivo on as many as five Ser/Thr residues. Phos‐phorylation might alter the dynamics of folding if the nascent polypeptide were phosphorylated in the cytoplasm. In particular, phosphorylation of Thr‐99 could neutralize cationic residues Lys‐106 and Arg‐108 within the hairpin loop. In addition, the methylation of Arg‐108 might stabilize the hairpin loop structure through hydrophobic interaction with the side chain of Pro‐97. The cationic side chains of arginine and lysine residues located on the faces of the β‐sheet (Arg‐43, Arg‐114, Lys‐13, Lys‐92, Lys‐153, and Lys‐156) could provide sites for interaction with phospholipids and other anionic structures on the surface of the myelin lipid bilayer.