Title

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

Student Author(s)

Sabrina S. Vollers

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date

2012-12-14

Document Type

Article

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.

Keywords

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

DOI of Published Version

10.1074/jbc.M112.369587

Source

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.

Journal/Book/Conference Title

The Journal of biological chemistry

Related Resources

Link to article in PubMed

PubMed ID

23093404

Link to Full Text

Share

COinS