Structural insights into antigen recognition of an anti-β-(1,6)-β-(1,3)-D-glucan antibody.
Structural insights into antigen recognition of an anti-β-(1,6)-β-(1,3)-D-glucan antibody.
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DOI：
10.1038/s41598-018-31961-x
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发表时间：
2018-09-12
影响因子：
4.6
通讯作者：
Rau U
中科院分区：
文献类型：
--
作者：
Sung KH;Josewski J;Dübel S;Blankenfeldt W;Rau U
裂殖酵母多糖(Schizophyllan，SCH)是一种由β-(1，3)-D-葡聚糖主链和支化的β-(1，6)-D-葡萄糖残基组成的高分子量多糖。它形成三股螺旋，对高温和极端pH高度稳定，这为SCH提供了工业和医疗应用的有趣特性。重组抗SCH抗体JoJ48C11识别SCH和相关的β-(1，6)-支链β-(1，3)-D-葡聚糖，但其特异性细节尚不清楚。在这里，我们通过测定JoJ48C11的抗原结合片段(FAB)的晶体结构来填补这一空白，分别以载脂蛋白的形式和与未支化的β-(1，3)-D-葡萄糖六聚体的络合物的晶体结构，分别以3.0和2.4 á的分辨率。结合对接研究，这使得构建了JoJ48C11/三螺旋SCH复合体，从而鉴定了JoJ48C11的八个氨基酸残基(Tyr27H，His35H，Trp47H，Trp100H，Asp105H；Asp49L，Lys52L，Trp90L)，这些氨基酸有助于识别SCH三螺旋的所有三条链上的葡萄糖单元。通过诱变和酶联免疫吸附分析证实了这些氨基酸的重要性。我们的工作解释了JoJ48C11对三螺旋β-(1，6)-支链β-(1，3)-D-葡聚糖的特异性识别，并为抗碳水化合物抗体提供了另一个结构实例。
Schizophyllan (SCH) is a high molecular weight homopolysaccharide composed of a β-(1,3)-D-glucan main chain with branching β-(1,6)-bound D-glucose residues. It forms triple helices that are highly stable towards heat and extreme pH, which provides SCH with interesting properties for industrial and medical applications. The recombinant anti-SCH antibody JoJ48C11 recognizes SCH and related β-(1,6)-branched β-(1,3)-D-glucans, but details governing its specificity are not known. Here, we fill this gap by determining crystal structures of the antigen binding fragment (Fab) of JoJ48C11 in the apo form and in complex with the unbranched β-(1,3)-D-glucose hexamer laminarihexaose 3.0 and 2.4 Å resolution, respectively. Together with docking studies, this allowed construction of a JoJ48C11/triple-helical SCH complex, leading to the identification of eight amino acid residues of JoJ48C11 (Tyr27H, His35H, Trp47H, Trp100H, Asp105H; Asp49L, Lys52L, Trp90L) that contribute to the recognition of glucose units from all three chains of the SCH triple helix. The importance of these amino acids was confirmed by mutagenesis and ELISA-based analysis. Our work provides an explanation for the specific recognition of triple-helical β-(1,6)-branched β-(1,3)-D-glucans by JoJ48C11 and provides another structure example for anti-carbohydrate antibodies.
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DOI：
10.1107/s090744491003982x
发表时间：
2011-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Evans PR
通讯作者：
Evans PR
DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
影响因子：
15
作者：
Hudson KL;Bartlett GJ;Diehl RC;Agirre J;Gallagher T;Kiessling LL;Woolfson DN
通讯作者：
Woolfson DN
影响因子：
14.9
作者：
Kim S;Thiessen PA;Bolton EE;Chen J;Fu G;Gindulyte A;Han L;He J;He S;Shoemaker BA;Wang J;Yu B;Zhang J;Bryant SH
通讯作者：
Bryant SH
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K