Identification of key amino acid residues determining ligand binding specificity, homodimerization and cellular distribution of human galectin-10
Identification of key amino acid residues determining ligand binding specificity, homodimerization and cellular distribution of human galectin-10
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确定人半乳糖凝集素 10 的配体结合特异性、同源二聚化和细胞分布的关键氨基酸残基的鉴定
DOI：
10.1093/glycob/cwy087
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发表时间：
2018-09
期刊：
影响因子：
4.3
通讯作者：
Zhou Yifa
中科院分区：
文献类型：
--
作者：
Su Jiyong;Song Chenyang;Si Yunlong;Cui Linlin;Yang Tong;Li Yuying;Wang Hao;Tai Guihua;Zhou Yifa
夏科 - 莱登晶体蛋白/半乳糖凝集素 - 10在嗜酸性粒细胞和嗜碱性粒细胞中大量表达，与多种免疫疾病相关。最近，晶体学和生物化学研究表明，半乳糖凝集素 - 10无法结合乳糖，原因在于一个谷氨酸残基（Glu33） 。
Charcot-Leyden crystal protein/Gal-10, abundantly expressed in eosinophils and basophils, is related to several immune diseases. Recently, crystallographic and biochemical studies showed that Gal-10 cannot bind lactose, because a glutamate residue (Glu33) from another monomer blocks the binding site. Moreover, Gal-10 actually forms a novel dimeric structure compared to other galectins. To investigate the role that Glu33 plays in inhibiting lactose binding, we mutated this residue to glutamine, aspartate, and alanine. The structure of E33A shows that Gal-10 can now bind lactose. In the hemagglutination assay, lactose could inhibit E33A from inducing chicken erythrocyte agglutination. Furthermore, we identified a tryptophan residue (Trp127) at the interface of homodimer that is crucial for Gal-10 dimerization. The variant W127A, which exists as a monomer, exhibited higher hemagglutination activity than wild type Gal-10. The solid phase assay also showed that W127A could bind to lactose-modified sepharose-6B, whereas wild type Gal-10 could not. This indicates that the open carbohydrate-binding site of the W127A monomer can bind to lactose. In addition, the distribution of EGFP-tagged Gal-10 and its variants in HeLa cells was investigated. Because Trp72 is the highly conserved in the ligand binding sites of galectins, we used EGFP-tagged W72A to show that Gal-10 could not be transported into the nucleus, indicating that Trp72 is crucial for Gal-10 transport into that organelle.
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影响因子：
20.3
作者：
Ann M. Dvorak;L. Letourneau;G. Login;Peter F. Weller;Steven J. Ackerman
通讯作者：
Ann M. Dvorak;L. Letourneau;G. Login;Peter F. Weller;Steven J. Ackerman
影响因子：
3.8
作者：
Than NG;Romero R;Xu Y;Erez O;Xu Z;Bhatti G;Leavitt R;Chung TH;El-Azzamy H;LaJeunesse C;Wang B;Balogh A;Szalai G;Land S;Dong Z;Hassan SS;Chaiworapongsa T;Krispin M;Kim CJ;Tarca AL;Papp Z;Bohn H
通讯作者：
Bohn H
影响因子：
2.9
作者：
Swaminathan;Leônidas;Savage;Ackerman;Acharya
通讯作者：
Swaminathan;Leônidas;Savage;Ackerman;Acharya
DOI：
10.2210/pdb1a3k/pdb
发表时间：
1998
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. Seetharaman;A. Kanigsberg;R. Slaaby;H. Leffler;S. Barondes;J. Rini
通讯作者：
J. Seetharaman;A. Kanigsberg;R. Slaaby;H. Leffler;S. Barondes;J. Rini
影响因子：
4.4
作者：
Dyer, KD;Handen, JS;Rosenberg, HF
通讯作者：
Rosenberg, HF