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Imaging Integrin Tension and Cellular Force at Submicron Resolution with an Integrative Tension Sensor
Published on: April 25, 2019
Integrin conformational regulation: uncoupling extension/tail separation from changes in the head region by a
Mattia Rocco1, Camillo Rosano, John W Weisel
1S.S. Biopolimeri e Proteomica, Istituto Nazionale per la Ricerca sul Cancro, IST c/o CBA, Genoa, Italy. mattia.rocco@istge.it
Structure (London, England : 1993)
|June 13, 2008
Summary
Integrins, crucial for cell adhesion, adopt extended conformations in their resting state, challenging previous models. Activation involves head region opening without immediate tail separation, revealing their complex plasticity.
Area of Science:
- Cell Biology
- Biophysics
- Structural Biology
Background:
- Integrin function relies on conformational changes, but their precise structures in resting and activated states are debated.
- Previous studies proposed bent resting states and extended, open states upon activation, with significant tail separation.
Purpose of the Study:
- To resolve controversies regarding integrin ectodomain conformations using hydrodynamic analysis.
- To investigate the structural rearrangements of alpha(v)beta(3) and alpha(IIb)beta(3) integrins during activation.
Main Methods:
- Experimental and computed hydrodynamics were employed to analyze atomic models of integrins.
- Comparison of hydrodynamic data with X-ray crystallography, NMR, and EM data.
Main Results:
- Hydrodynamics indicate that resting integrins (alpha(v)beta(3) and alpha(IIb)beta(3)) are already in an extended conformation.
- Ligand binding to alpha(v)beta(3) induces head opening (hybrid domain swing-out) without tail separation.
- Priming agents cause conformational changes in alpha(IIb)beta(3) consistent with head opening and transmembrane helix shifts.
Conclusions:
- Resting integrins are extended, contrary to some crystallographic data.
- Integrin activation involves nuanced conformational changes, including head region opening, rather than a simple extension and tail separation.
- Integrin plasticity is finely tuned, with distinct mechanisms for extension and activation-induced rearrangements.
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