Related Experiment Video
Updated: Aug 20, 2026

Imaging Integrin Tension and Cellular Force at Submicron Resolution with an Integrative Tension Sensor
Published on: April 25, 2019
Conversion between three conformational states of integrin I domains with a C-terminal pull spring studied with
Moonsoo Jin1, Ioan Andricioaei, Timothy A Springer
1The CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Abstract:
We test with molecular dynamics the hypothesis that interdomain forces in integrins, simulated with a spring attached to the C-terminal alpha 7-helix of an integrin I domain, can allosterically stabilize alternative I domain conformations. Depending on the force applied and timecourse, in alpha(L) and alpha(M) I domains the beta 6-alpha 7 loop moves successively between three ratchet positions; i.e. from closed to intermediate, and then to open. More distal, linked alterations in MIDAS loops and metal coordination closely resemble those seen when the MIDAS becomes ligated. Simulations show that the intermediate state is populated over a wider range of forces for alpha(L) than alpha(M) I domains. Simulations with mutant I domains suggest that specific ratchet residues regulate conformational equilibria. Simulations with alpha(1) and alpha(2) I domains reveal a lack of the intermediate conformation, owing to Phe to Glu substitution at the second ratchet residue. The findings have important implications for biological regulation of integrin adhesiveness.
Related Concept Videos
Activation of Integrins
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.
Integrins
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,...
Intracellular Signaling Affects Focal Adhesions
Some...
¹H NMR of Conformationally Flexible Molecules: Temporal Resolution
Tension Response at Adherens Junctions
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...
Assembly of Signaling Complexes
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...

