Glucose transporter oligomeric structure determines transporter function. Reversible redox-dependent interconversions of tetrameric and dimeric GLUT1
Biochemistry & Molecular Pharmacology
Department of Biochemistry and Molecular Pharmacology; Program in Molecular Medicine
Biochemistry, Biophysics, and Structural Biology | Life Sciences | Medicine and Health Sciences
This study investigates the relationship between human erythrocyte glucose transport protein (GLUT1) oligomeric structure and glucose transporter function. Oligomeric structure was analyzed by hydrodynamic studies of cholate-solubilized GLUT1, by chemical cross-linking studies of membrane-resident GLUT1 and by using conformation-specific antibodies. Transporter function (substrate binding) was analyzed by equilibrium cytochalasin B and D-glucose binding measurements. Erythrocyte-resident glucose transporter is a GLUT1 homotetramer, binds 1 mol of cytochalasin B/2 mol of GLUT1, and presents at least two binding sites to D-glucose. Native structure and function appear to be stabilized by intramolecular disulfide bonds and are preserved during GLUT1 purification by the omission of reductant. Native structure is independent of in vitro and in vivo membrane GLUT1 density but is transformed to dimeric GLUT1 by alkaline reduction. Dimeric GLUT1 binds 1 mol of cytochalasin B/mol of GLUT1, presents a single population of binding sites to D-glucose, and is obtained upon GLUT1 purification in the presence of reductant. Native structure and function are restored by treatment of dimeric GLUT1 with glutathione-disulfide (K0.5 glutathione disulfide = 29 microM). We propose that native structure is established prior to transporter translocation to the plasma membrane and that intrasubunit disulfide bonds promote cooperative subunit interactions that stabilize transporter structure and function.
J Biol Chem. 1992 Nov 25;267(33):23829-38.
The Journal of biological chemistry
Hebert, Daniel N. and Carruthers, Anthony, "Glucose transporter oligomeric structure determines transporter function. Reversible redox-dependent interconversions of tetrameric and dimeric GLUT1" (1992). GSBS Student Publications. 7.