The core trisaccharide of an N-linked glycoprotein intrinsically accelerates folding and enhances stability
The core trisaccharide of an N-linked glycoprotein intrinsically accelerates folding and enhances stability
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DOI：
10.1073/pnas.0810318105
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发表时间：
2009-03-03
影响因子：
11.1
通讯作者：
Powers, Evan T.
中科院分区：
文献类型：
--
作者：
Hanson, Sarah R.;Culyba, Elizabeth K.;Powers, Evan T.
系统地研究了人免疫细胞分化受体簇2（hCD 2ad）的单-N-糖基化粘附结构域的折叠能量学，以了解N-聚糖对折叠能量景观的影响。相对于非糖基化蛋白质，充分阐述的N-聚糖结构使折叠加速4倍，并使β-夹心结构稳定3.1 kcal/mol。N-聚糖的第一个糖单元负责整个折叠加速和2/3的天然状态稳定。剩余的三分之一的稳定化作用来自接下来的2个糖单元。因此，保守的N-连接丙糖核心ManGlcNAc（2）改善了蛋白质折叠的动力学和热力学。由N-糖基化赋予的折叠的天然状态稳定化和降低的激活屏障提供了用于增强分泌途径中的折叠的强大且潜在的一般机制。
The folding energetics of the mono-N-glycosylated adhesion domain of the human immune cell receptor cluster of differentiation 2 (hCD2ad) were studied systematically to understand the influence of the N-glycan on the folding energy landscape. Fully elaborated N-glycan structures accelerate folding by 4-fold and stabilize the beta-sandwich structure by 3.1 kcal/mol, relative to the nonglycosylated protein. The N-glycan's first saccharide unit accounts for the entire acceleration of folding and for 2/3 of the native state stabilization. The remaining third of the stabilization is derived from the next 2 saccharide units. Thus, the conserved N-linked triose core, ManGlcNAc(2), improves both the kinetics and the thermodynamics of protein folding. The native state stabilization and decreased activation barrier for folding conferred by N-glycosylation provide a powerful and potentially general mechanism for enhancing folding in the secretory pathway.