Crystal structure of a glucose/H+ symporter and its mechanism of action

Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):17862-7. doi: 10.1073/pnas.1311485110. Epub 2013 Oct 14.

Abstract

Glucose transporters are required to bring glucose into cells, where it is an essential energy source and precursor in protein and lipid synthesis. These transporters are involved in important common diseases such as cancer and diabetes. Here, we report the crystal structure of the Staphylococcus epidermidis glucose/H(+) symporter in an inward-facing conformation at 3.2-Å resolution. The Staphylococcus epidermidis glucose/H(+) symporter is homologous to human glucose transporters, is very specific and has high avidity for glucose, and is inhibited by the human glucose transport inhibitors cytochalasin B, phloretin, and forskolin. On the basis of the crystal structure in conjunction with mutagenesis and functional studies, we propose a mechanism for glucose/H(+) symport and discuss the symport mechanism versus facilitated diffusion.

Keywords: GLUT; major facilitator superfamily; membrane protein; solute-carrier 2A; sugar transporter.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport / physiology
  • Cloning, Molecular
  • Colforsin / pharmacology
  • Crystallization
  • Cytochalasin B / pharmacology
  • Escherichia coli
  • Glucose Transport Proteins, Facilitative / antagonists & inhibitors*
  • Glucose Transport Proteins, Facilitative / chemistry*
  • Glucose Transport Proteins, Facilitative / genetics
  • Humans
  • Models, Molecular*
  • Mutagenesis
  • Mutagenesis, Site-Directed
  • Phloretin / pharmacology
  • Protein Conformation*
  • Sequence Homology
  • Staphylococcus epidermidis / chemistry*
  • Staphylococcus epidermidis / genetics

Substances

  • Glucose Transport Proteins, Facilitative
  • Colforsin
  • Cytochalasin B
  • Phloretin

Associated data

  • PDB/4LDS