Yan Renhong, Li Yaning, Shi Yi, Zhou Jiayao, Lei Jianlin, Huang Jing, Zhou Qiang
Key Laboratory of Structural Biology of Zhejiang Province, Institute of Biology, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province, China.
Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Sci Adv. 2020 Apr 15;6(16):eaay6379. doi: 10.1126/sciadv.aay6379. eCollection 2020 Apr.
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 bAT (SLC7A9) is a representative light chain of HATs, forming heterodimer with rBAT, a heavy chain which mediates the membrane trafficking of bAT. The bAT-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 bAT-rBAT complex alone and in complex with arginine substrate at resolution of 2.7 and 2.3 Å, respectively. The overall structure of bAT-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.
异源氨基酸转运体（HATs）催化氨基酸的跨膜转运，由通过二硫键连接的重链和轻链两个亚基组成。bAT（SLC7A9）是HATs的代表性轻链，与rBAT形成异二聚体，rBAT是一种重链，介导bAT的膜转运。bAT-rBAT复合物是一种必需的交换体，介导胱氨酸和阳离子氨基酸的流入以及中性氨基酸在肾脏和小肠中的流出。在这里，我们分别报道了人bAT-rBAT复合物单独存在以及与精氨酸底物结合时的冷冻电镜结构，分辨率分别为2.7 Å和2.3 Å。bAT-rBAT的整体结构以异二聚体的二聚体形式存在，与之前的研究一致。一个配体分子结合在底物结合口袋附近，在该口袋附近发现了一个封闭口袋，我们发现它对底物转运很重要。
