The human solute carriers (SLCs) comprise over 400 different transporters, organized into 65 families (http://slc.bioparadigms.org/) based on their sequence homology and transport function. SLCs are responsible for transporting extraordinarily diverse solutes across biological membranes, including inorganic ions, amino acids, lipids, sugars, neurotransmitters and drugs. Most of these membrane proteins function as coupled symporters (co-transporters) utilizing downhill ion (H⁺ or Na⁺) gradients as the driving force for the transport of substrate against its concentration gradient into cells. Other members work as antiporters (exchangers) that typically contain a single substrate-binding site with an alternating access mode of transport, while a few members exhibit channel-like properties. Dysfunction of SLCs is correlated with numerous human diseases and therefore they are potential therapeutic drug targets. In this review, we identified all of the SLC crystal structures that have been determined, most of which are from prokaryotic species. We further sorted all the SLC structures into four main groups with different protein folds and further discuss the well-characterized MFS (major facilitator superfamily) and LeuT (leucine transporter) folds. This review provides a systematic analysis of the structure, molecular basis of substrate recognition and mechanism of action in different SLC family members.

人类溶质运载体（SLC）包含400多种不同的转运蛋白，根据它们的序列同源性和转运功能分为65个家族（http://slc.bioparadigms.org/）。SLC负责跨生物膜运输极其多样的溶质，包括无机离子，氨基酸，脂质，糖，神经递质和药物。这些膜蛋白大多数都利用下坡离子（H ⁺或Na ⁺）作为偶联的共转运蛋白（共转运蛋白）。）梯度作为底物相对于其浓度梯度向细胞内转运的驱动力。其他成员充当反向转运蛋白（交换子），通常包含单个底物结合位点，具有交替的运输方式，而少数成员表现出类似通道​​的特性。SLC的功能障碍与多种人类疾病相关，因此它们是潜在的治疗药物靶标。在这篇综述中，我们确定了所有已确定的SLC晶体结构，其中大多数来自原核生物。我们进一步将所有SLC结构分为具有不同蛋白质折叠的四个主要组，并进一步讨论了特征明确的MFS（主要促进子超家族）和LeuT（亮氨酸转运蛋白）折叠。这篇评论对结构进行了系统的分析，