Sequence composition predicts immunoglobulin superfamily members that could share the intrinsically disordered properties of antibody CH1 domains.
Sequence composition predicts immunoglobulin superfamily members that could share the intrinsically disordered properties of antibody CH1 domains.
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DOI：
10.1038/s41598-017-12616-9
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发表时间：
2017-09-29
影响因子：
4.6
通讯作者：
Warwicker J
中科院分区：
文献类型：
--
作者：
Hebditch M;Curtis R;Warwicker J
抗体是日益增长的蛋白质治疗领域的核心，而且它们越来越多地被作为片段和组合来操纵。更好地理解抗体结构域在分离中的性质将有助于它们的工程设计。我们对结构数据库中的抗体和Fab片段的序列和结构域相互作用进行了分析。在所研究的序列相关性质中，发现CH1和CL的相对赖氨酸和精氨酸含量高于可变区。由于早期的工作表明，在更易溶的蛋白质中，赖氨酸比精氨酸更受青睐，这表明单个结构域可能没有优化以获得更大的溶解度，这为片段工程提供了空间。在其他基于序列的特征中，CH1是异常的。一种基于序列的方案预测CH1将被折叠，尽管已知CH1折叠与IgG的组装和分泌有关。计算表明，与其他FAB结构域相比，CH1结构域中的电荷相互作用对折叠状态稳定性的贡献较小。扩展到免疫球蛋白超家族，我们发现非抗体结构域的一个子集与CH1具有相同的序列组成属性，这使得我们认为其中一些也可能耦合折叠、组装和分泌。
Antibodies are central to the growing sector of protein therapeutics, and increasingly they are being manipulated as fragments and combinations. An improved understanding of the properties of antibody domains in isolation would aid in their engineering. We have conducted an analysis of sequence and domain interactions for IgG antibodies and Fab fragments in the structural database. Of sequence-related properties studied, relative lysine to arginine content was found to be higher in CH1 and CL than in variable domains. As earlier work shows that lysine is favoured over arginine in more soluble proteins, this suggests that individual domains may not be optimised for greater solubility, giving scope for fragment engineering. Across other sequence-based features, CH1 is anomalous. A sequence-based scheme predicts CH1 to be folded, although it is known that CH1 folding is linked to IgG assembly and secretion. Calculations indicate that charge interactions in CH1 domains contribute less to folded state stability than in other Fab domains. Expanding to the immunoglobulin superfamily reveals that a subset of non-antibody domains shares sequence composition properties with CH1, leading us to suggest that some of these may also couple folding, assembly and secretion.
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影响因子：
16
作者：
Feige, Matthias J.;Groscurth, Sandra;Marcinowski, Moritz;Shimizu, Yuichiro;Kessler, Horst;Hendershot, Linda M.;Buchner, Johannes
通讯作者：
Buchner, Johannes
免疫球蛋白重链和结合蛋白络合物通过轻链添加在体内分离。
影响因子：
7.8
作者：
Hendershot, L M
通讯作者：
Hendershot, L M
影响因子：
7.8
作者：
Hendershot, L;Bole, D;Kohler, G;Kearney, J F
通讯作者：
Kearney, J F
Biopython：用于计算分子生物学和生物信息学的免费 Python 工具。
DOI：
10.1093/bioinformatics/btp163
发表时间：
2009-06-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Cock PJ;Antao T;Chang JT;Chapman BA;Cox CJ;Dalke A;Friedberg I;Hamelryck T;Kauff F;Wilczynski B;de Hoon MJ
通讯作者：
de Hoon MJ
影响因子：
2.9
作者：
BASHFORD, D;KARPLUS, M
通讯作者：
KARPLUS, M