The impact of exchanging the light and heavy chains on the structures of bovine ultralong antibodies.

IF 1.1 4区 生物学 Q4 BIOCHEMICAL RESEARCH METHODS
John D Clarke, Alice Douangamath, Halina Mikolajek, Marie Bonnet-Di Placido, Jingshan Ren, Elizabeth E Fry, Dave I Stuart, John A Hammond, Raymond J Owens
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引用次数: 0

Abstract

The third complementary-determining regions of the heavy-chain (CDR3H) variable regions (VH) of some cattle antibodies are highly extended, consisting of 48 or more residues. These `ultralong' CDR3Hs form β-ribbon stalks that protrude from the surface of the antibody with a disulfide cross-linked knob region at their apex that dominates antigen interactions over the other CDR loops. The structure of the Fab fragment of a naturally paired bovine ultralong antibody (D08), identified by single B-cell sequencing, has been determined to 1.6 Å resolution. By swapping the D08 native light chain with that of an unrelated antigen-unknown ultralong antibody, it is shown that interactions between the CDR3s of the variable domains potentially affect the fine positioning of the ultralong CDR3H; however, comparison with other crystallographic structures shows that crystalline packing is also a major contributor. It is concluded that, on balance, the exact positioning of ultralong CDR3H loops is most likely to be due to the constraints of crystal packing.

交换轻链和重链对牛超长抗体结构的影响。
一些牛抗体的重链可变区(CDR3H)的第三个互补决定区(VH)高度延伸,由 48 个或更多残基组成。这些 "超长 "的 CDR3H 形成从抗体表面伸出的 β 带状茎,其顶端有一个二硫化物交联的旋钮区,与其他 CDR 环相比,该旋钮区在抗原相互作用中占主导地位。通过单 B 细胞测序确定的自然配对牛超长抗体(D08)的 Fab 片段的结构分辨率达到了 1.6 Å。通过将 D08 原生轻链与无相关抗原的未知超长抗体的轻链互换,结果表明可变结构域的 CDR3 之间的相互作用可能会影响超长抗体 CDR3H 的精细定位;然而,与其他晶体学结构的比较表明,晶体堆积也是一个主要因素。结论是,总的来说,超长 CDR3H 环的精确定位最有可能是由于晶体堆积的限制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Acta crystallographica. Section F, Structural biology communications
Acta crystallographica. Section F, Structural biology communications BIOCHEMICAL RESEARCH METHODSBIOCHEMISTRY &-BIOCHEMISTRY & MOLECULAR BIOLOGY
CiteScore
1.90
自引率
0.00%
发文量
95
期刊介绍: Acta Crystallographica Section F is a rapid structural biology communications journal. Articles on any aspect of structural biology, including structures determined using high-throughput methods or from iterative studies such as those used in the pharmaceutical industry, are welcomed by the journal. The journal offers the option of open access, and all communications benefit from unlimited free use of colour illustrations and no page charges. Authors are encouraged to submit multimedia content for publication with their articles. Acta Cryst. F has a dedicated online tool called publBio that is designed to make the preparation and submission of articles easier for authors.
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