Post-translational hydroxylation at the N-terminus of the prion protein reveals presence of PPII structure in vivo
Post-translational hydroxylation at the N-terminus of the prion protein reveals presence of PPII structure in vivo
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DOI：
10.1093/emboj/19.20.5324
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发表时间：
2000-10-16
期刊：
影响因子：
11.4
通讯作者：
Hope, J
中科院分区：
文献类型：
--
作者：
Gill, AC;Ritchie, MA;Hope, J
传染性海绵状脑病的特征是宿主蛋白PrPC（细胞朊病毒蛋白）转化为蛋白酶抗性同种型PrPSc（朊病毒蛋白瘙痒症同种型）。PrP的高度灵活的N-末端区域的重要性最近变得更加广泛地受到重视，特别是与其金属离子结合结构域及其形成聚（L-脯氨酸）II（PPII）螺旋的潜力相关的生物活性。N-末端肽PrP 37 -53的圆二色性光谱表明，PPII螺旋在水性缓冲液中形成;由于它还含有Xaa-Pro-Gly共有序列，因此它可以作为胶原修饰酶脯氨酰4-羟化酶的底物。这种修饰的直接证据是通过质谱和Edman测序获得的重组小鼠PrP分泌稳定转染的中国仓鼠卵巢细胞。几乎完全转换的脯氨酸4-羟脯氨酸发生在残基Pro44的这种鼠蛋白;相同的羟基化残基检测到，在较低的水平，在PrPSc从羊瘙痒症感染的小鼠的大脑。PrP的该区域的阳离子结合和/或翻译后羟基化可以调节其在细胞的生理学和病理学中的作用。
The transmissible spongiform encephalopathies are characterized by conversion of a host protein, PrPC (cellular prion protein), to a protease-resistant isoform, PrPSc (prion protein scrapie isoform). The importance of the highly flexible, N-terminal region of PrP has recently become more widely appreciated, particularly the biological activities associated with its metal ion-binding domain and its potential to form a poly(L-proline) II (PPII) helix. Circular dichroism spectroscopy of an N-terminal peptide, PrP37-53, showed that the PPII helix is formed in aqueous buffer; as it also contains an Xaa-Pro-Gly consensus sequence, it may act as a substrate for the collagen-modifying enzyme prolyl 4-hydroxylase. Direct evidence for this modification was obtained by mass spectrometry and Edman sequencing in recombinant mouse PrP secreted from stably transfected Chinese hamster ovary cells. Almost complete conversion of proline to 4-hydroxyproline occurs specifically at residue Pro44 of this murine protein; the same hydroxylated residue was detected, at lower levels, in PrPSc from the brains of scrapie-infected mice. Cation binding and/or post-translational hydroxylation of this region of PrP may regulate its role in the physiology and pathobiology of the cell.