PDF(Pubmed)
Abstract：
Borate transporters are membrane transport proteins that regulate intracellular borate levels. In plants, borate is a micronutrient essential for growth but is toxic in excess, while in yeast, borate is unnecessary for growth and borate export confers tolerance. Borate transporters share structural homology with human bicarbonate transporters in the SLC4 family despite low sequence identity and differences in transported solutes. Here, we characterize the S. cerevisiae borate transporter Bor1p and examine whether key biochemical features of SLC4 transporters extend to borate transporters. We show that borate transporters and SLC4 transporters share multiple properties, including lipid-promoted dimerization, sensitivity to stilbene disulfonate-derived inhibitors, and a requirement for an acidic residue at the solute binding site. We also identify several amino acids critical for Bor1p function and show that disease-causing mutations in human SLC4A1 will eliminate in vivo function when their homologous mutations are introduced in Bor1p. Our data help elucidate mechanistic features of Bor1p and reveal significant functional properties shared between borate transporters and SLC4 transporters.
摘要：
硼酸盐转运蛋白是调节细胞内硼酸盐水平的膜转运蛋白。在植物中,硼酸盐是生长必需的微量营养素，但过量有毒，而在酵母中，硼酸盐对于增长是不必要的，硼酸盐出口赋予了容忍度。硼酸盐转运蛋白与SLC4家族中的人碳酸氢盐转运蛋白具有结构同源性，尽管序列同一性低并且转运溶质存在差异。这里,我们描述了酿酒酵母硼酸盐转运蛋白Bor1p，并检查SLC4转运蛋白的关键生化特征是否延伸到硼酸盐转运蛋白。我们证明硼酸盐转运蛋白和SLC4转运蛋白具有多种特性，包括脂质促进的二聚化，对二苯乙烯二磺酸盐衍生抑制剂的敏感性，以及对溶质结合位点处的酸性残基的要求。我们还鉴定了对Bor1p功能至关重要的几种氨基酸，并表明当将其同源突变引入Bor1p时，人类SLC4A1中的致病突变将消除体内功能。我们的数据有助于阐明Bor1p的机械特征，并揭示硼酸盐转运蛋白和SLC4转运蛋白之间共有的重要功能特性。
