Related Experiment Video
Updated: Jun 20, 2026
09:56
Tension Gauge Tether Probes for Quantifying Growth Factor Mediated Integrin Mechanics and Adhesion
Published on: February 11, 2022
Integrin activation dynamics between the RGD-binding site and the headpiece hinge.
Eileen Puklin-Faucher1, Viola Vogel1
1Department of Materials, Laboratory of Biologically Oriented Materials, ETH, Zurich CH-8049, Switzerland.
The Journal of Biological Chemistry
|September 19, 2009
Summary
Integrin activation involves a conformational change. Molecular dynamics simulations reveal a linked structural pathway, showing how ligand binding and force influence this process, with calcium ions affecting affinity.
Area of Science:
- Biochemistry
- Structural Biology
- Biophysics
Background:
- Integrins mediate cell adhesion by linking extracellular matrix to the cytoskeleton.
- Integrin activation relies on allosteric conformational changes, but the signal propagation pathway is unclear.
Purpose of the Study:
- To elucidate the structural events and dynamic pathways of integrin activation using molecular dynamics simulations.
- To investigate the role of ligand binding, force, and divalent cations in integrin conformational changes.
Main Methods:
- Molecular dynamics simulations of the alpha(V)beta(3) integrin headpiece bound to FnIII(10).
- Analysis of allosteric communication pathways and the influence of ligand-mediated force and metal ions.
Main Results:
- A hydrophobic T-junction linking the ligand-binding pocket to the betaA/hybrid domain hinge was identified.
- This T-junction formation is induced by ligand binding and hinge opening, exhibiting bidirectionality.
- Ligand-mediated force accelerates T-junction formation, while Ca(2+) instead of Mg(2+) at the ADMIDAS site inhibits it.
Conclusions:
- The study provides a unified structural model for integrin activation dynamics.
- Findings explain how ligand binding, force, and divalent cations cooperatively regulate integrin function.
- This work bridges molecular dynamics simulations with experimental data on integrin catch bonds and affinity modulation.
More Related Videos
Related Concept Videos
01:15Activation of Integrins
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
01:10Integrins
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
01:22Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
01:14Rab Proteins
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...