Abstract
Facilitative transport of glucose across the plasma membrane of mammalian cells is mediated by members of the glucose transporter (GLUT) proteins which possess 12 membrane-spanning helical segments. These proteins show tissue- and cell-specific expression and exhibit distinct kinetic and regulatory properties that reflect their specific functional roles. Six members of the GLUT family have already been described. This review summarizes recent advances concerning structure and function of the GLUT protein. Structure function relationship of the HepG2/erythrocyte-type glucose transporter (GLUT1) has been studied by in vitro site-directed mutagenesis. In a highly-conserved QQXSGXNXXXYY in transmembrane helix 7, Gln282 has been shown to be involved in a recognition of the outside-specific ligand, such as ATB-BMPA. Tyr293→I1e mutant GLUT1 has been shown to be locked into an outward-facing conformation and Tyr293 in the edge of this motif is involved in closing the exofacial site in the transport catalysis process. These observations suggested that transmembrane helix 7 has an important role in ligand recognition as well as in transport catalysis . Mutagenesis at Pro385 in transmembrane helix 10 has been carried out and reduction in transport and exofacial ATB-BMPA photolabeling occur as the result of substitution with isoleucine, suggesting that retention of flexibility in this region is required for the transport catalysis process. Mutation in either Trp388 or Trp412 residue resulted in reduced transport activity while only Trp388 mutant expressed in oocytes showed a marked reduction in the affinity for cytochalasin B. Examinations by C-terminally truncated transporters revealed that the infracellular C-terminus of GLUTI also contributes to the glucose transport process .
