Structure and function of the Na+/glucose cotransporter.
Cotransporters are a major class of membrane transport proteins that are responsible for the accumulation of nutrients, neurotransmitters, osmolytes and ions in cells from bacteria to man. The energy for solute accumulation comes from the proton and/or sodium electrochemical gradients that exist across cell membranes. A major problem in biology is how transport is coupled to these electrochemical potential gradients. The primary example of this class of membrane proteins is the intestinal brush border Na+/glucose cotransporter (SGLT1), first described by Bob Crane in 1960. Over 35 members of the SGLT1 gene family have been identified in animal cells, yeast and bacteria, and all share a common core structure of 13 transmembrane (TM) helices. Electrophysiological techniques have been used to examine the function of several family members, chimeras and mutants expressed in heterologous systems such as Xenopus laevis oocytes. These have revealed that cotransporters are multi-functional proteins: they are responsible for 1). uncoupled passive Na+ transport (Na+ uniport); 2). down-hill water transport in the absence of substrate; 3). Na+/substrate cotransport; and 4). Na+/substrate/water cotransport. The sugar binding and translocation pathway is formed by 4 TM helices near the C-terminal of the protein, helices 10-13. We propose that the N-terminal domains of SGLT1 are responsible for Na+ binding and/or translocation, and that Na+/glucose cotransport results from interactions between the N- and C-terminal domains of the protein.
Wright
E M
EM
Department of Physiology, UCLA Medical Center 90095-1751, USA.
Loo
D D
DD
Panayotova-Heiermann
M
M
Hirayama
B A
BA
Turk
E
E
Eskandari
S
S
Lam
J T
JT
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D004594:Electrophysiology; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D009004:Monosaccharide Transport Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D011487:Protein Conformation; D051269:Sodium-Glucose Transporter 1; D013329:Structure-Activity Relationship; D014867:Water / Q000378:metabolism
D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; C495674:SLC5A1 protein, human; D051269:Sodium-Glucose Transporter 1; D014867:Water