An evolutionarily ancient Oatp: insights into conserved functional domains of these proteins
An evolutionarily ancient Oatp: insights into conserved functional domains of these proteins
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DOI：
10.1152/ajpgi.00458.2001
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发表时间：
2002-04-01
影响因子：
4.5
通讯作者：
Boyer, JL
中科院分区：
文献类型：
--
作者：
Cai, SY;Wang, W;Boyer, JL
细胞对有机溶质的摄取在很大程度上是由称为 OATP (SLC21A) 的膜转运蛋白基因家族介导的。为了研究 SLC21A 家族的结构决定因素和进化发展，我们从小鳐鱼 Raja erinacea 的肝脏中克隆了一个高度表达的进化原始 Oatp，并对其进行了功能表征。获得了编码 689 个氨基酸的蛋白质的全长 cDNA (2.3 kb)。这种新型skate Oatp的特征，包括组织表达、亚细胞定位、底物选择性、Na+依赖性和抑制剂选择性，与肝脏特异性的人OATP-C和大鼠Oatp4大致相似。然而，与其他 OATP 的序列比较表明，该 Skate Oatp 仅与肝脏特异性 OATP/Oatp 以及人 OATP-F 具有相似的 40-50% 氨基酸同一性。进一步的计算机分析显示，最高的氨基酸同一性位于第一个外部环 (78%) 和内部环 (75%) 以及跨膜结构域 2 (76%)、3 (62%)、4 (70%) 和 11 (64%)。我们认为 SLC21A 转运蛋白家族的保守区域可能是底物特异性和功能的关键结构决定因素。
Cellular uptake of organic solutes is mediated in large part by a gene family of membrane transporters called OATPs (SLC21A). To study the structural determinants and evolutionary development of the SLC21A family, we have cloned and functionally characterized a highly expressed evolutionarily primitive Oatp from the liver of the small skate, Raja erinacea. A full-length cDNA (2.3 kb) was obtained that encodes a protein of 689 amino acids. The characteristics of this novel skate Oatp, including tissue expression, subcellular localization, substrate selectivity, Na+ dependence, and inhibitor selectivity were generally similar to liver-specific human OATP-C and rat Oatp4. However, sequence comparisons with other OATPs indicate that this skate Oatp shares only similar to40-50% amino acid identity with the liver-specific OATPs/Oatps and with human OATP-F. Further computer analysis revealed that the highest amino acid identities reside in the first external (78%) and internal loops (75%) and transmembrane domains 2 (76%), 3 (62%), 4 (70%), and 11 (64%). We propose that the conserved regions of the SLC21A transporter family may be critical structural determinants of substrate specificity and function.