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

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2012 Oct 25

PMID 23093404

Citations 17

Authors

Sabrina S Vollers

Anthony Carruthers

Affiliations

Soon will be listed here.

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.

Citing Articles

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