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人肌肉型烟碱型乙酰胆碱受体α1亚基高抗原性且具有天然样折叠的细胞外结构域的表达，适用于重症肌无力的抗原特异性治疗。

Expression of a highly antigenic and native-like folded extracellular domain of the human α1 subunit of muscle nicotinic acetylcholine receptor, suitable for use in antigen specific therapies for Myasthenia Gravis.

作者信息

Niarchos Athanasios, Zouridakis Marios, Douris Vassilis, Georgostathi Assimina, Kalamida Dimitra, Sotiriadis Alexandros, Poulas Konstantinos, Iatrou Kostas, Tzartos Socrates J

机构信息

Department of Pharmacy, University of Patras, Patras, Greece.

Department of Biochemistry, Hellenic Pasteur Institute, Athens, Greece.

出版信息

PLoS One. 2013 Dec 20;8(12):e84791. doi: 10.1371/journal.pone.0084791. eCollection 2013.

DOI:10.1371/journal.pone.0084791
PMID:24376846
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3869910/
Abstract

We describe the expression of the extracellular domain of the human α1 nicotinic acetylcholine receptor (nAChR) in lepidopteran insect cells (i-α1-ECD) and its suitability for use in antigen-specific therapies for Myasthenia Gravis (MG). Compared to the previously expressed protein in P. pastoris (y-α1-ECD), i-α1-ECD had a 2-fold increased expression yield, bound anti-nAChR monoclonal antibodies and autoantibodies from MG patients two to several-fold more efficiently and resulted in a secondary structure closer to that of the crystal structure of mouse α1-ECD. Our results indicate that i-α1-ECD is an improved protein for use in antigen-specific MG therapeutic strategies.

摘要

我们描述了人α1烟碱型乙酰胆碱受体（nAChR）胞外结构域在鳞翅目昆虫细胞中的表达（i-α1-ECD）及其在重症肌无力（MG）抗原特异性治疗中的适用性。与先前在巴斯德毕赤酵母中表达的蛋白（y-α1-ECD）相比，i-α1-ECD的表达产量提高了2倍，与抗nAChR单克隆抗体和MG患者的自身抗体结合效率提高了2至数倍，并且其二级结构更接近小鼠α1-ECD的晶体结构。我们的结果表明，i-α1-ECD是用于抗原特异性MG治疗策略的改良蛋白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6351/3869910/aecc93dbe37d/pone.0084791.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6351/3869910/778c0468df66/pone.0084791.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6351/3869910/2264fe1d2a4b/pone.0084791.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6351/3869910/aecc93dbe37d/pone.0084791.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6351/3869910/778c0468df66/pone.0084791.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6351/3869910/2264fe1d2a4b/pone.0084791.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6351/3869910/aecc93dbe37d/pone.0084791.g003.jpg

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