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Membrane-mediated structural transitions at the cytoplasmic face during integrin activation
Olga Vinogradova1, Julia Vaynberg, Xiangming Kong
1Structural Biology Program, Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Summary
Integrin tails unlatch and embed into membranes, changing structure to enable cell signaling. Talin binding further separates tails, revealing mechanisms of integrin activation.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Integrin inside-out activation is crucial for transmembrane signal transduction.
- The dissociation of integrin cytoplasmic tails is implicated, but the dynamic process on the membrane surface is unclear.
Purpose of the Study:
- To elucidate the dynamic structural changes of integrin cytoplasmic tails during activation.
- To understand the role of membrane interactions in integrin signaling.
Main Methods:
- Utilized membrane-mimetic micelles to study integrin cytoplasmic tail behavior.
- Investigated structural changes using biophysical techniques.
- Examined the role of Talin in tail dissociation and membrane binding.
Main Results:
- Integrin alpha/beta cytoplasmic tails embed into membrane-mimetic micelles upon unlatching, inducing significant structural alterations.
- The beta3 tail possesses a C-terminal membrane binding site (NPLY motif) and interacts with Talin.
- Talin binding promotes cytoplasmic tail separation along the membrane surface.
Conclusions:
- Membrane embedding and Talin binding are critical for integrin cytoplasmic tail separation and activation.
- These findings provide a structural basis for membrane-mediated regulation of integrin activation and signaling.