Probing the structure and function of the human erythrocyte glucose transporter.

Abstract

Introduction Recent I )NA cloning studies have revealed the existence of a large family o f homologous solute transporters (the ‘sugar transporter’ family) in organisms as diverse as mammals. plants, fungi and bacteria [ 11. These proteins catalyse the transport of ;I mide range o f substrates. including not only monosaccharides and disaccharides, but also iionsugar molecules such as tricx-boxylic acids and a variety of antibiotics and antiseptic agents [2] . Interestingly, the fhii ly contains examples of both passive transporters, typified by the human erythrocyte monosaccharide transport protein [ 3 1, and active trmsporters such ;IS the galactose/I I + symporter of Escherichiu coli [ 4 I , and the Mg’+ -tetracycline/l I + antiporters o f (;ram-negative bacteria [ 21. The most intensively studied member of the family is the facilitated diffusion transporter for glucose and other monosaccharides that is found in the human rrythrocyte membrane (GI,[ J‘I’I in the terminology of Fukunioto et al. 151) 101. This 492-residue integral membrane protein is widely distributed in mammalian tissues. but is most abundant in those w i t h a barrier function. such as the placental syncytiotrophoblast 171 and the blood-brain barrier [ X 1. l1nlike other members of the family. it can readily be purified in functionally active form on a large scale [ 0 I , and so represents an ideal model system for investigating the molecular mechanism of transport in the family as a w hole. I Iere. I describe recent advances in our understanding of the transport mechanism, derived both from examination of the aligned amino acid sequences of the family niemhers. and from biochemical experiments on the purified human protein. Although such approaches