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A two-step mechanism for sugar translocation
Do-Hwan Ahn1, Claudia Alleva1,2, Tom Reichenbach1
1Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden.
Nature Structural & Molecular Biology
|April 8, 2026
Summary
Sugar transporters like glucose transporters (GLUTs) have specific substrate preferences. This study reveals that the transporter
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biophysics
Background:
- Mammalian glucose transporters (GLUTs) are crucial for sugar distribution.
- The bacterial xylose transporter (XylE) is a model for GLUTs, but exhibits different substrate specificity.
- Understanding transporter specificity is key to metabolic research.
Purpose of the Study:
- To elucidate the molecular basis of substrate specificity in sugar transporters.
- To differentiate between transported substrates and inhibitors using biophysical techniques.
- To identify key structural determinants of transporter specificity.
Main Methods:
- Saturation Transfer Difference (STD) Nuclear Magnetic Resonance (NMR) spectroscopy.
- Protein engineering of the xylose transporter (XylE).
- Molecular dynamics simulations.
- Biochemical assays and structural analysis of GLUTs.
Main Results:
- STD NMR signals distinguish transported sugars from inhibitors.
- Transported sugars generate STD signals, while inhibitors do not.
- Engineering XylE's binding pocket and TM7b helix enabled glucose transport.
- TM7b was identified as crucial for occluded state formation in transporters.
Conclusions:
- Transporter specificity is determined by the formation of a substrate-induced transition-state intermediate, not initial binding.
- The TM7b helix plays a critical role in regulating transporter conformation and specificity.
- This work provides new insights into the mechanism of sugar transport and GLUT function.
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