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Structure, function and regulation of mammalian glucose transporters of the SLC2 family
Pflügers Archiv - European Journal of Physiology ( IF 2.9 ) Pub Date : 2020-06-26 , DOI: 10.1007/s00424-020-02411-3
Geoffrey D. Holman

The SLC2 genes code for a family of GLUT proteins that are part of the major facilitator superfamily (MFS) of membrane transporters. Crystal structures have recently revealed how the unique protein fold of these proteins enables the catalysis of transport. The proteins have 12 transmembrane spans built from a replicated trimer substructure. This enables 4 trimer substructures to move relative to each other, and thereby alternately opening and closing a cleft to either the internal or the external side of the membrane. The physiological substrate for the GLUTs is usually a hexose but substrates for GLUTs can include urate, dehydro-ascorbate and myo-inositol. The GLUT proteins have varied physiological functions that are related to their principal substrates, the cell type in which the GLUTs are expressed and the extent to which the proteins are associated with subcellular compartments. Some of the GLUT proteins translocate between subcellular compartments and this facilitates the control of their function over long- and short-time scales. The control of GLUT function is necessary for a regulated supply of metabolites (mainly glucose) to tissues. Pathophysiological abnormalities in GLUT proteins are responsible for, or associated with, clinical problems including type 2 diabetes and cancer and a range of tissue disorders, related to tissue-specific GLUT protein profiles. The availability of GLUT crystal structures has facilitated the search for inhibitors and substrates and that are specific for each GLUT and that can be used therapeutically. Recent studies are starting to unravel the drug targetable properties of each of the GLUT proteins.



中文翻译:

SLC2家族的哺乳动物葡萄糖转运蛋白的结构,功能和调控

SLC2这些基因编码一个家族的GLUT蛋白,它们是膜转运蛋白的主要促进子超家族(MFS)的一部分。最近的晶体结构揭示了这些蛋白质独特的蛋白质折叠如何使运输催化成为可能。这些蛋白质具有12个跨膜跨度,这些跨膜跨度是由复制的三聚体亚结构构建的。这使得4个三聚体子结构能够相对于彼此移动,从而交替地打开和关闭在膜的内侧或外侧的裂缝。GLUT的生理底物通常是己糖,但GLUT的底物可包括尿酸盐,脱氢抗坏血酸盐和肌醇。GLUT蛋白具有与其主要底物有关的多种生理功能,表达GLUT的细胞类型以及蛋白质与亚细胞区室结合的程度。某些GLUT蛋白在亚细胞区室之间转运,这有助于长期和短期内控制其功能。GLUT功能的控制对于调节代谢产物(主要是葡萄糖)向组织的供应是必需的。GLUT蛋白的病理生理异常是导致或与包括与组织特异性GLUT蛋白谱有关的2型糖尿病和癌症以及一系列组织疾病在内的临床问题有关的。GLUT晶体结构的可用性促进了抑制剂和底物的寻找,并且这些抑制剂和底物对每种GLUT都是特异性的并且可以用于治疗。

更新日期:2020-09-01
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