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首页> 外文期刊>Biochemistry >Rapid release and unusual stability of immunodominant peptide 45-89 from citrullinated myelin basic protein.
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Rapid release and unusual stability of immunodominant peptide 45-89 from citrullinated myelin basic protein.

机译：从瓜氨酸化的髓鞘碱性蛋白中快速释放和显性的免疫优势肽4​​5-89。

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摘要

Myelin basic protein (MBP) exists in a population of isoforms and isomers. The 18.5 kDa MBP-C1, the main human adult isoform, has 170 residues and is relatively unmodified, whereas the same isoform can be citrullinated on six arginine residues to create the MBP-C8 (MBP Cit6) isomer. MBP Cit6 dominates in MS brain, accounting for 45% rather than 25% of the population of MBP isomers. In the fulminant form of MS, known as Marburg's Disease, 18 of the 19 arginines in MBP are citrullinated (MBP Cit18). Citrullination of MBP could lead to instability of myelin or limited remyelination. In this investigation, the susceptibilities to degradation by cathepsin D of MBP Cit6 and MBP-C1, both from normal and MS brain tissue, and Marburg MBP Cit18 were compared. The pattern of digestion was similar, and no differences of corresponding isomers in normal and MS brain were noted. However, normal MBP Cit6 was degraded 10-fold more rapidly than MBP-C1, and MBP Cit18 was degraded even more rapidly. MBP peptide 45-89 was preserved regardless of isomer type or source. Its generation was directly related to the citrulline content of the MBP substrate being 4 times faster in normal MBP Cit6 and 35 times faster in Marburg MBP Cit18 than in normal MBP-C1. Peptide 45-89 from a citrullinated MBP exhibited more deamidation, and, regardless of source, showed an alpha-helix structure in a lipid mimetic environment. We postulate that the generation of MBP peptides, including those that are dominant and encephalitogenic, is directly related to deimination of arginine to citrulline in MBP.
机译：髓磷脂碱性蛋白（MBP）存在于同工型和异构体中。 18.5 kDa MBP-C1是人类的主要成年同工型，具有170个残基，并且相对未修饰，而相同的同工型可以在6个精氨酸残基上瓜氨酸化，从而生成MBP-C8（MBP Cit6）异构体。 MBP Cit6在MS脑中占主导地位，占MBP异构体总数的45％，而不是25％。在MS的爆发形式（称为Marburg病）中，MBP的19个精氨酸中有18个被瓜氨酸化（MBP Cit18）。 MBP的瓜氨酸化可能导致髓磷脂不稳定或髓鞘再生受限。在这项研究中，比较了组织蛋白酶D对正常和MS脑组织以及Marburg MBP Cit18对MBP Cit6和MBP-C1进行组织蛋白酶D降解的敏感性。消化模式相似，在正常脑和MS脑中未发现相应异构体的差异。但是，正常的MBP Cit6的降解速度比MBP-C1快10倍，而MBP Cit18的降解速度甚至更快。不论异构体类型或来源如何，MBP肽45-89均被保留。它的产生与MBP底物的瓜氨酸含量直接相关，在正常MBP Cit6中，瓜氨酸含量是正常MBP-C1中的4倍，在Marburg MBP Cit18中是35倍。来自瓜氨酸化的MBP的肽45-89表现出更多的脱酰胺作用，并且不管来源如何，在脂质模拟环境中都表现出α-螺旋结构。我们推测MBP肽的产生，包括占优势和致脑炎的肽，与MBP中精氨酸向瓜氨酸的直接化作用有关。

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