GSBS Student Publications
Title
Sequence Determinants of GLUT1-mediated Accelerated-exchange Transport: Analysis by Homology-Scanning Mutagenesis
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
Keywords
glucose transport; membrane proteins; membrane transport; mutagenesis; sugar transport
Journal Title
The Journal of biological chemistry
PubMed ID
23093404
Repository Citation
Vollers, Sabrina S. and Carruthers, Anthony, "Sequence Determinants of GLUT1-mediated Accelerated-exchange Transport: Analysis by Homology-Scanning Mutagenesis" (2012). GSBS Student Publications. 1801.
https://escholarship.umassmed.edu/gsbs_sp/1801