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Membrane Phase-Dependent Occlusion of Intramolecular GLUT1 Cavities Demonstrated by Simulations
Javier Iglesias-Fernandez1, Peter J Quinn2, Richard J Naftalin3
1Department of Chemistry, School of Medicine, King's College London, London, United Kingdom.
Biophysical Journal
|March 30, 2017
Summary
Cooling the cell membrane alters its physical state, impacting glucose transporter 1 (GLUT1) function. Membrane phase changes reduce transporter channel size, decreasing glucose transport. This highlights how membrane environment affects protein structure and dynamics.
Area of Science:
- Biophysics
- Structural Biology
- Membrane Transport
Background:
- Glucose transporter 1 (GLUT1) activity is closely linked to cell membrane composition and physical state.
- Cooling transitions membrane lipids from a fluid to a gel phase, significantly decreasing glucose transport rates.
Purpose of the Study:
- To investigate how the physical phase of the membrane influences the structural dynamics of the glucose transporter GLUT1.
- To understand the mechanisms by which membrane phase transitions affect transporter function.
Main Methods:
- Utilized molecular-dynamics simulations to model the effects of membrane phase changes on GLUT1.
- Simulated a transition from a fluid to a gel membrane phase to observe structural alterations.
Main Results:
- Simulations showed that transitioning to a gel phase reduced the size of cavities and tunnels within GLUT1.
- These structural changes, particularly in transport pathways, were primarily driven by membrane alterations, not just protein cooling.
- In silico cooling of the membrane alone mimicked uniform cooling effects on protein structure and dynamics.
Conclusions:
- The structure and dynamics of GLUT1 are sensitive to the physical phase of the surrounding membrane.
- These findings have significant implications for understanding how transmembrane proteins respond to their biophysical environment.