Stoner G L
J Neurochem. 1984 Aug;43(2):433-47. doi: 10.1111/j.1471-4159.1984.tb00919.x.
Predictions of myelin basic protein secondary structure have not previously considered a major role for beta-structure in the organization of the native molecule because optical rotatory dispersion and circular dichroism studies have provided little, if any, evidence for beta-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 beta-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 beta-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 antiparallel beta-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 alpha-helices, but each of the two large loops could accommodate an alpha-helix. Myelin basic protein is known to be phosphorylated in vivo on as many as five Ser/Thr residues. Phosphorylation 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 beta-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.
此前，髓鞘碱性蛋白二级结构的预测未考虑β结构在天然分子组织中的主要作用，原因如下：旋光色散和圆二色性研究几乎没有（即便有也极少）提供β结构的证据，而且聚阳离子蛋白通常被认为难以折叠成紧密结构。然而，Chou-Fasman、Lim和Robson算法在氨基酸序列中总共识别出五条β链。其中四条疏水氨基酸序列（37 - 45、87 - 95、110 - 118和150 - 158）可形成一个发夹中间体，启动希腊钥匙型β结构的折叠。在更疏水的一侧进行第二次折叠，并从N端（残基13 - 21）添加一条链，将完成五链反平行β折叠片层。通过对疏水残基进行定相，可以预测出独特的链排列。髓鞘碱性蛋白异常的三脯氨酸序列（100 - 102）包含在14个残基的发夹环中。如果这些脯氨酸处于反式构象，模型显示在残基102 - 105（脯氨酸 - 丝氨酸 - 谷氨酰胺 - 甘氨酸）处可能会出现一个反向转角。算法在α螺旋的预测上存在分歧，但两个大环中的每一个都可以容纳一个α螺旋。已知髓鞘碱性蛋白在体内多达五个丝氨酸/苏氨酸残基上发生磷酸化。如果新生多肽在细胞质中被磷酸化，磷酸化可能会改变折叠动力学。特别是，苏氨酸 - 99的磷酸化可能会中和发夹环内的阳离子残基赖氨酸 - 106和精氨酸 - 108。此外，精氨酸 - 108的甲基化可能通过与脯氨酸 - 97的侧链进行疏水相互作用来稳定发夹环结构。位于β折叠片层表面的精氨酸和赖氨酸残基的阳离子侧链（精氨酸 - 43、精氨酸 - 114、赖氨酸 - 13、赖氨酸 - 92、赖氨酸 - 153和赖氨酸 - 156）可为与髓鞘脂质双层表面的磷脂和其他阴离子结构相互作用提供位点。
