Statistical analysis of the protein environment of N-glycosylation sites:: implications for occupancy, structure, and folding
Statistical analysis of the protein environment of N-glycosylation sites:: implications for occupancy, structure, and folding
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DOI：
10.1093/glycob/cwh008
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发表时间：
2004-02-01
期刊：
影响因子：
4.3
通讯作者：
Wormald, MR
中科院分区：
文献类型：
--
作者：
Petrescu, AJ;Milac, AL;Wormald, MR
我们最近报道了对糖苷键结构数据的统计分析。在这里，我们将这种分析扩展到糖-蛋白质连接，以及N-糖基化位点周围的肽的一级、二级和三级结构。我们调查了蛋白质数据库中的506个糖蛋白，得到了2592个糖基化序列(占1683个)，并生成了一个由626个非冗余序列组成的数据库，其中386个占了。被占据的天冬酰胺周围的预期氨基酸组成发生了偏差，特别是天冬酰胺和苏氨酸在+2位出现更多的芳香族残基。糖基化改变了天冬酰胺侧链的扭转角分布，降低了其灵活性。发现二级结构发生变化的糖基化位点的概率增加。建立了一个11类分类来描述糖基化位点周围的蛋白质表面几何形状。33%的被占用部位位于裸露的凸面上，10%位于深凹槽中，20%位于凹槽边缘，多糖填充裂隙。数量惊人的糖基化天冬酰胺残基的可及性很低。在折叠过程中，与多糖密切接触的芳香族氨基酸的发生率高于其在表面或蛋白质核心的正常水平。这些数据对控制序列占据和糖基化位点的进化选择具有重要意义，并讨论了蛋白质折叠稳定的机制和蛋白质折叠的区域质量控制。蛋白质-多糖的疏水性相互作用和折叠蛋白质中糖基化位点的低可及性是常见的特征，可能在调节这些功能中起关键作用。
We recently reported statistical analysis of structural data on glycosidic linkages. Here we extend this analysis to the glycan-protein linkage, and the peptide primary, secondary, and tertiary structures around N-glycosylation sites. We surveyed 506 glycoproteins in the Protein Data Bank crystallographic database, giving 2592 glycosylation sequons (1683 occupied) and generated a database of 626 nonredundant sequons with 386 occupied. Deviations in the expected amino acid composition were seen around occupied asparagines, particularly an increased occurrence of aromatic residues before the asparagine and threonine at position +2. Glycosylation alters the asparagine side chain torsion angle distribution and reduces its flexibility. There is an elevated probability of finding glycosylation sites in which secondary structure changes. An 11-class taxonomy was developed to describe protein surface geometry around glycosylation sites. Thirty-three percent of the occupied sites are on exposed convex surfaces, 10% in deep recesses and 20% on the edge of grooves with the glycan filling the cleft. A surprisingly large number of glycosylated asparagine residues have a low accessibility. The incidence of aromatic amino acids brought into close contact with the glycan by the folding process is higher than their normal levels on the surface or in the protein core. These data have significant implications for control of sequon occupancy and evolutionary selection of glycosylation sites and are discussed in relation to mechanisms of protein fold stabilization and regional quality control of protein folding. Hydrophobic protein-glycan interactions and the low accessibility of glycosylation sites in folded proteins are common features and may be critical in mediating these functions.