Cryo-EM structure of the human heteromeric amino acid transporter b0,+ AT-rBAT
Cryo-EM structure of the human heteromeric amino acid transporter b0,+ AT-rBAT
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DOI：
10.1126/sciadv.aay6379
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发表时间：
2020-04-01
期刊：
影响因子：
13.6
通讯作者：
Zhou, Qiang
中科院分区：
文献类型：
--
作者：
Yan, Renhong;Li, Yaning;Zhou, Qiang
异聚体氨基酸转运蛋白（HAT）催化氨基酸的跨膜运动，其包括通过二硫桥连接的两个亚基，重链和轻链。B（0，+）AT（SLC 7A 9）是HAT的代表性轻链，与rBAT形成异源二聚体，rBAT是介导B（0，+）AT的膜运输的重链。B（0，+）AT-rBAT复合物是一种专性交换体，介导胱氨酸和阳离子氨基酸在肾脏和小肠的内流以及中性氨基酸的外排。在这里，我们报告的cryo-EM结构的人B（0，+）AT-rBAT复合物单独和复合精氨酸底物的分辨率分别为2.7和2.3埃。B（0，+）AT-rBAT的总体结构以异二聚体的二聚体形式存在，与之前的研究一致。一个配体分子被绑定到底物结合口袋，附近的闭塞口袋被确定，我们发现，这是重要的底物运输。
Heteromeric amino acid transporters (HATs) catalyze the transmembrane movement of amino acids, comprising two subunits, a heavy chain and a light chain, linked by a disulfide bridge. The b(0,+)AT (SLC7A9) is a representative light chain of HATs, forming heterodimer with rBAT, a heavy chain which mediates the membrane trafficking of b(0,+)AT. The b(0,+)AT-rBAT complex is an obligatory exchanger, which mediates the influx of cystine and cationic amino acids and the efflux of neutral amino acids in kidney and small intestine. Here, we report the cryo-EM structure of the human b(0,+)AT-rBAT complex alone and in complex with arginine substrate at resolution of 2.7 and 2.3 angstrom, respectively. The overall structure of b(0,+)AT-rBAT exists as a dimer of heterodimer consistent with the previous study. A ligand molecule is bound to the substrate binding pocket, near which an occluded pocket is identified, to which we found that it is important for substrate transport.