C-mannosylation supports folding and enhances stability of thrombospondin repeats
C-mannosylation supports folding and enhances stability of thrombospondin repeats
复制标题
C-甘露糖基化支持折叠并增强血小板反应蛋白重复序列的稳定性
作者：
Aleksandra Shcherbakova;M. Preller;M. Taft;Jordi Pujols;S. Ventura;Birgit Tiemann;Falk F. R. Buettner;H. Bakker
先前的研究证明了 C-甘露糖基化对于有效蛋白质分泌的重要性。为了研究其对蛋白质折叠和稳定性的影响，我们分析了 netrin 受体 UNC-5 的 C-甘露糖基化和非 C-甘露糖基化血小板反应蛋白 1 型重复序列 (TSR)。在没有 C-甘露糖基化的情况下，UNC-5 TSR 只能在低温下获得，并且很大一部分显示出不正确的分子间二硫键桥接，而当 C-甘露糖基化时几乎观察不到这种情况。糖基化 TSR 对热和还原变性过程表现出更高的抵抗力，并且 C-甘露糖的存在促进了还原和变性 TSR 的体外氧化折叠。分子动力学模拟支持了实验研究，并表明 C-甘露糖可以参与分子内氢键并限制 TSR 色氨酸-精氨酸阶梯的灵活性。我们提出，在内质网折叠过程中，C-甘露糖定向下面的色氨酸残基并促进色氨酸-精氨酸阶梯的形成，从而影响半胱氨酸和二硫键桥的定位。
Previous studies demonstrated importance of C-mannosylation for efficient protein secretion. To study its impact on protein folding and stability, we analyzed both C-mannosylated and non-C-mannosylated thrombospondin type 1 repeats (TSRs) of netrin receptor UNC-5. In absence of C-mannosylation, UNC-5 TSRs could only be obtained at low temperature and a significant proportion displayed incorrect intermolecular disulfide bridging, which was hardly observed when C-mannosylated. Glycosylated TSRs exhibited higher resistance to thermal and reductive denaturation processes, and the presence of C-mannoses promoted the oxidative folding of a reduced and denatured TSR in vitro. Molecular dynamics simulations supported the experimental studies and showed that C-mannoses can be involved in intramolecular hydrogen bonding and limit the flexibility of the TSR tryptophan-arginine ladder. We propose that in the endoplasmic reticulum folding process, C-mannoses orient the underlying tryptophan residues and facilitate the formation of the tryptophan-arginine ladder, thereby influencing the positioning of cysteines and disulfide bridging.
人备解素的分子结构，补体替代途径的正调节剂。
DOI：
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发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Smith,CA;Pangburn,MK;Vogel,CW;Müller-Eberhard,HJ
通讯作者：
Müller-Eberhard,HJ