N-Glycosylation as a Tool to Study Antithrombin Secretion, Conformation, and Function.
N-Glycosylation as a Tool to Study Antithrombin Secretion, Conformation, and Function.
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DOI：
10.3390/ijms22020516
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发表时间：
2021-01-06
影响因子：
5.6
通讯作者：
Martínez-Martínez I
中科院分区：
文献类型：
--
作者：
Águila S;Noto R;Luengo-Gil G;Espín S;Bohdan N;de la Morena-Barrio ME;Peñas J;Rodenas MC;Vicente V;Corral J;Manno M;Martínez-Martínez I
n -链糖基化是涉及蛋白质折叠、功能和清除的关键翻译后修饰。n -链糖基化也用于治疗，以提高许多蛋白质的半衰期。抗凝血酶是一种具有四个潜在n -糖基化位点的蛇形蛋白，在止血中起着关键作用，其缺乏会显著增加血栓形成的风险。在这项研究中，我们利用引入n -糖基化位点作为工具来探索这种糖基化对蛋白质折叠、分泌和这种关键抗凝血剂功能的影响。为了完成这项任务，我们在每条链中引入了一个额外的n -糖基化序列。有趣的是，所有可能快速折叠或被赖氨酸包围的区域都没有糖基化，即使存在n -糖基化序列。A-和b -片上的新序列减少了分泌，b -片对这些变化更敏感。然而，C-sheet链上的突变允许正确的折叠和分泌，从而导致功能性变异。因此，我们的研究揭示了抗凝血酶分泌的关键区域，并可能适用于所有蛇蛋白。这些结果也可以帮助我们了解导致i型缺陷的自然变异的功能影响。
N-linked glycosylation is a crucial post-translational modification involved in protein folding, function, and clearance. N-linked glycosylation is also used therapeutically to enhance the half-lives of many proteins. Antithrombin, a serpin with four potential N-glycosylation sites, plays a pivotal role in hemostasis, wherein its deficiency significantly increases thrombotic risk. In this study, we used the introduction of N-glycosylation sites as a tool to explore what effect this glycosylation has on the protein folding, secretion, and function of this key anticoagulant. To accomplish this task, we introduced an additional N-glycosylation sequence in each strand. Interestingly, all regions that likely fold rapidly or were surrounded by lysines were not glycosylated even though an N-glycosylation sequon was present. The new sequon in the strands of the A- and B-sheets reduced secretion, and the B-sheet was more sensitive to these changes. However, the mutations in the strands of the C-sheet allowed correct folding and secretion, which resulted in functional variants. Therefore, our study revealed crucial regions for antithrombin secretion and could potentially apply to all serpins. These results could also help us understand the functional effects of natural variants causing type-I deficiencies.
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DOI：
10.1002/prot.340230412
发表时间：
1995-12-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Frishman, D;Argos, P
通讯作者：
Argos, P
DOI：
10.1073/pnas.1004785107
发表时间：
2010-10-05
影响因子：
11.1
作者：
Ekeowa, Ugo I.;Freeke, Joanna;Lomas, David A.
通讯作者：
Lomas, David A.
影响因子：
10.4
作者：
Mushunje, A;Evans, G;Zhou, A
通讯作者：
Zhou, A
影响因子：
15.9
作者：
Lomas, DA;Mahadeva, R
通讯作者：
Mahadeva, R
影响因子：
4.8
作者：
Izaguirre, G;Olson, ST
通讯作者：
Olson, ST