N-连接糖蛋白的核心三糖本质上可加速折叠并增强稳定性。
The core trisaccharide of an N-linked glycoprotein intrinsically accelerates folding and enhances stability.
作者信息
Hanson Sarah R, Culyba Elizabeth K, Hsu Tsui-Ling, Wong Chi-Huey, Kelly Jeffery W, Powers Evan T
机构信息
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
出版信息
Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3131-6. doi: 10.1073/pnas.0810318105. Epub 2009 Feb 9.
Abstract
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.
摘要
为了解N-聚糖对折叠能量景观的影响，我们系统地研究了人类免疫细胞分化簇2（hCD2ad）的单N-糖基化粘附结构域的折叠能量学。相对于非糖基化蛋白，完全成熟的N-聚糖结构使折叠速度加快4倍，并使β-三明治结构稳定3.1千卡/摩尔。N-聚糖的第一个糖单元负责折叠的全部加速以及天然态稳定的2/3。稳定的其余三分之一来自接下来的2个糖单元。因此，保守的N-连接三糖核心ManGlcNAc(2)改善了蛋白质折叠的动力学和热力学。N-糖基化赋予的天然态稳定和降低的折叠活化能垒为增强分泌途径中的折叠提供了一种强大且可能通用的机制。
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