The GLUT Family The human genome co

The GLUT Family
The human genome contains 14 members of the GLUT family(Fig. 2), which can be divided into 3 subfamilies according to sequence similarities and
3.1 characteristic elements 26 The members of the GLUT family(gene name SLC2A) exhibit a striking tissue specific expression 1,3 .Moreover, they differ in their functional characteristics(eg, their substrate specific ity, their Km values, and their binding-affinities to the inhibitory ligands cytochalasin B and forskolin) Fur thermore, the function of some transporters(eg, GLUT4) is modified by a regulated redistribution of the protein between the cell membrane and an intracellu lar compartment. These different characteristics allow a complex and specific regulation of glucose uptake according to the cellular requirements and the physio logic conditions of substrate supply.
As early as 1985, Mueckler et al suggested a struc tural model of a facilitative glucose transporter accord ing to a hydropathy plot of the GLUT1. This model was later supported by the results of a glycosylation scan ning study. According to this model, the GLUT pro teins comprise the 12 hydrophobic, transmembrane o-helices arranged in a way that the C-terminus and the N terminus are facing the cytoplasm. Recently,Lemieux et all succeeded in crystallizing a structur ally related protein, the glycerol-3-phosphate trans porter of Escherichia coli, and obtained a 3-dimen sional structure that confirmend the proposed model of the GLUT proteins and of all other related transport- ers. Sequence comparisons of GLUT1 to 4 and site- directed mutations performed in GLUT1 and GLUT4 allowed the definition of characteristic sugar trans porter signatures: (a) 7 conserved glycine residues within the helices, (b) several basic and acidic residues in the surface of the proteins, (c) 2 conserved trypto- phan residues, and(d) 2 conserved tyrosine residues 26.