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Functional unfolding of the integrin αX transmembrane helix
Han N Vu1, Minhyeong Lee2, Alan J Situ1
1Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033.
Summary
Integrin proteins can partially unfold their transmembrane helices, altering cell adhesion. This unfolding mechanism allows integrins to sense membrane properties and regulate leukocyte functions like phagocytosis.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Proteins in biological membranes adopt specific structures like alpha-helices or beta-barrels to span lipid bilayers.
- These structures maintain hydrogen bonding to avoid unfavorable interactions between polar backbone atoms and the hydrophobic membrane core.
Purpose of the Study:
- To investigate the structural dynamics of integrin transmembrane (TM) helices, specifically integrin alphaX and alphaM.
- To understand how TM helix structure influences integrin function and cell adhesion.
- To explore the potential for TM helices to act as sensors of membrane properties.
Main Methods:
- Analysis of integrin alphaX and alphaM TM helix structure and dynamics.
- Investigating the impact of TM helix unfolding on integrin subunit association.
- Assessing the role of membrane geometry in modulating TM helix unfolding.
Main Results:
- Integrin alphaX and alphaM TM helices partially unfold at the N-terminal region.
- This partial unfolding creates a dynamic, frayed helix that weakens the interaction with the beta2 subunit.
- The degree of unfolding is influenced by membrane geometry, suggesting a sensing mechanism.
Conclusions:
- Integrin alphaX and alphaM deviate from the typical membrane protein structure paradigm by partially unfolding their TM helices.
- This structural plasticity modulates integrin activation thresholds and cell adhesion, particularly in leukocyte phagocytosis.
- TM helix backbone dynamics offer a mechanism for sensing membrane properties and regulating protein function.
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