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Study on_the protein-protein interaction regulating the function of amino acid transporters

蛋白质-蛋白质相互作用调节氨基酸转运蛋白功能的研究

基本信息

批准号：
17590226
负责人：
KANAI Yoshikatsu
金额：
$ 2.24万
依托单位：
Kyorin University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Heterodimeric amino acid transporters are formed by disulfide bonding of a twelve-membrane spanning protein (catalytic subunit) and a single membrane spanning protein (regulatory subunit). We have performed BLAST searches of human and mouse genome data bases using amino acid sequences of LAT1, BAT1 and CAT1 as queries. We have found 5 new genes, SLC7-N1-5, as new members of SLC7 family. By searching EST (expressed sequence tag) data bases, we have concluded that two of them (SLC7 N4 and SLC7 N5) are pseudogenes, because they never appear in EST data bases. SLC7 -N1 possesses 12 transmembrane domains and is supposed to be a catalytic subunit of heterodimeric amino acid transporters. We have named it AGT 1. AGT 1 protein is found on the basolateral membrane of proximal and distal tubules of mouse kidney. Because AGT 1 is supposed to be linked with unknown regulatory subunit, we have generated fusion proteins in which AGT 1 is connected with known regulatory subunits 4F2hc or rBAT and expressed them in Xenopus oocytes. The fusion proteins appear on the plasma membrane and exhibit the transport of acidic amino acids. SLC7 N2 possesses 14 transmembrane domains and exhibits particularly high affinity to arginine, thus we named it CATS (cationic amino acid transporter 5). CAT5 is expressed in the syncytio-trophoblast of mouse placenta and supposed to mediate transport of amino acids through the placental bather as well as to supply placental cells with arginine as a precursor of NO synthesis. SLC7 N3 also possesses 14 transmembrane domains and transports small neutral amino acids as well as small basic amino acids, thus we have named it y^+Asc-1. In this study, the function of all the members of heterodimeric amino acid transporter family has been revealed. The results of this study would provide essential information to establish the basis for the genome-wide analyses of diseases or pathological conditions and facilitate drug design targeting the transporters of interest.

异二聚体氨基酸转运体是由一个跨膜蛋白（催化亚基）和一个跨膜蛋白（调节亚基）的二硫键结合形成的。我们使用LAT1、BAT1和CAT1的氨基酸序列对人类和小鼠基因组数据库进行BLAST检索。我们发现SLC7家族新成员SLC7- n1 -5 5个基因。通过对EST（表达序列标签）数据库的检索，我们发现其中两个基因（SLC7 N4和SLC7 N5）是假基因，因为它们从未在EST数据库中出现过。SLC7 -N1具有12个跨膜结构域，被认为是异二聚体氨基酸转运体的催化亚基。我们把它命名为agt1。在小鼠肾近端和远端小管的基底外膜上发现了agt1蛋白。由于AGT - 1被认为与未知的调控亚基相连接，我们已经生成了AGT - 1与已知的调控亚基4F2hc或rBAT相连接的融合蛋白，并在非洲爪蟾卵母细胞中表达。融合蛋白出现在质膜上，并表现出酸性氨基酸的运输。SLC7 N2具有14个跨膜结构域，对精氨酸具有特别高的亲和力，因此我们将其命名为CATS（阳离子氨基酸转运蛋白5）。CAT5在小鼠胎盘的合胞滋养细胞中表达，被认为介导氨基酸通过胎盘池的运输，并为胎盘细胞提供精氨酸作为NO合成的前体。SLC7 N3还具有14个跨膜结构域，并能运输小的中性氨基酸和小的碱性氨基酸，因此我们将其命名为y^+Asc-1。本研究揭示了异二聚体氨基酸转运蛋白家族所有成员的功能。这项研究的结果将为疾病或病理状况的全基因组分析奠定基础，并促进针对感兴趣的转运蛋白的药物设计提供必要的信息。