GSBS Student Publications

Title

Sequence Determinants of GLUT1-mediated Accelerated-exchange Transport: Analysis by Homology-Scanning Mutagenesis

Student Author(s)

Sabrina S. Vollers

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Date

12-14-2012

Document Type

Article

Medical Subject Headings

Glucose Transporter Type 1; Glucose Transporter Type 4; Mutagenesis; Protein Conformation; Biological Transport

Disciplines

Biochemistry | Molecular Biology | Structural Biology

Abstract

The class 1 equilibrative glucose transporters GLUT1 and GLUT4 are structurally similar but catalyze distinct modes of transport. GLUT1 exhibits trans-acceleration, in which the presence of intracellular sugar stimulates the rate of unidirectional sugar uptake. GLUT4-mediated uptake is unaffected by intracellular sugar. Using homology-scanning mutagenesis in which domains of GLUT1 are substituted with equivalent domains from GLUT4 and vice versa, we show that GLUT1 transmembrane domain 6 is both necessary and sufficient for trans-acceleration. This region is not directly involved in GLUT1 binding of substrate or inhibitors. Rather, transmembrane domain 6 is part of two putative scaffold domains, which coordinate membrane-spanning amphipathic helices that form the sugar translocation pore. We propose that GLUT1 transmembrane domain 6 restrains import when intracellular sugar is absent by slowing transport-associated conformational changes.

Rights and Permissions

Vollers SS, Carruthers A. Sequence Determinants of GLUT1-mediated Accelerated-exchange Transport: Analysis by Homology-Scanning Mutagenesis. J Biol Chem. 2012 Dec 14;287(51):42533-44. doi: 10.1074/jbc.M112.369587. Epub 2012 Oct 23.

DOI of Published Version

10.1074/jbc.M112.369587

Related Resources

Link to article in PubMed

Keywords

glucose transport; membrane proteins; membrane transport; mutagenesis; sugar transport

Journal Title

The Journal of biological chemistry

PubMed ID

23093404