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Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads
Published on: March 8, 2017
Key interactions in integrin ectodomain responsible for global conformational change detected by elastic network
Atsushi Matsumoto1, Tetsuji Kamata, Junichi Takagi
1Quantum Bioinformatics Team, Center for Computational Science and Engineering, Japan Atomic Energy Agency, 8-1 Umemidai, Kizugawa, Kyoto 619-0215, Japan. matsumoto.atsushi@jaea.go.jp
Biophysical Journal
|June 3, 2008
Summary
Integrins undergo large structural changes upon activation. Specific interactions involving key residues stabilize the bent form of integrin alpha(V)beta(3), a mechanism unique to certain integrin types.
Area of Science:
- Biochemistry
- Structural Biology
- Cell Biology
Background:
- Integrins are crucial membrane proteins mediating cell-cell and cell-extracellular matrix interactions in metazoans.
- While some integrins exhibit large conformational changes upon activation, the precise mechanisms and their prevalence remain unclear.
Purpose of the Study:
- To elucidate the activation mechanism of integrins by investigating the structural dynamics of integrin alpha(V)beta(3).
- To identify key residues and interactions responsible for maintaining the integrin's bent conformation.
Main Methods:
- Normal-mode analysis using an elastic network model was performed on the integrin alpha(V)beta(3) ectodomain.
- Iterative calculations identified key residues influencing molecular motion.
- Mutation experiments on integrin alpha(IIb)beta(3) verified the role of these residues.
Main Results:
- Specific nonbonded interactions involving identified key residues act as a "snap" mechanism, stabilizing the bent conformation of integrin alpha(V)beta(3).
- Mutation experiments confirmed the critical role of these residues in the conformational change.
- Analysis of residue conservation across the integrin family revealed that this specific stabilizing mechanism is present only in limited groups of integrin beta-chains.
Conclusions:
- The study reveals a unique molecular mechanism stabilizing the bent conformation of integrin alpha(V)beta(3).
- This interaction-based mechanism is not universally conserved, suggesting distinct activation pathways among different integrin types.
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