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Updated: Jan 22, 2026

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Published on: October 4, 2024

Modulating Integrin αIIbβ3 Activity through Mutagenesis of Allosterically Regulated Intersubunit Contacts.

Sophia K Tan¹, Karen P Fong², Nicholas F Polizzi¹

¹Department of Pharmaceutical Chemistry , University of California, San Francisco , San Francisco , California 94158 , United States.

|July 3, 2019

Summary

This summary is machine-generated.

Altering specific sites in the integrin αIIbβ3 stalk interface with alanine can cause constant platelet activation. This study reveals how interaction geometry influences protein stability and integrin function.

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Electromechanical Assessment of Optogenetically Modulated Cardiomyocyte Activity

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Published on: March 5, 2020

Area of Science:

Biochemistry
Molecular Biology
Structural Biology

Background:

Integrin αIIbβ3 is crucial for platelet aggregation, transitioning from an inactive to an active state upon stimulation.
The interaction between the αIIb and β3 extracellular stalks stabilizes the inactive integrin conformation and dissociates upon activation.

Purpose of the Study:

To investigate the role of specific amino acid interactions in the αIIbβ3 stalk interface.
To determine the structural basis for constitutive integrin αIIbβ3 activation through targeted mutations.

Main Methods:

Site-directed mutagenesis introducing alanine substitutions at sensitive positions within the αIIbβ3 stalk interface.
Structural bioinformatics analysis to assess the impact of mutations on intersubunit contacts and interaction geometry.

Main Results:

Alanine replacements in the stalk interface destabilized the inactive integrin conformation, leading to constitutive activation.
Perturbing favorable intersubunit contacts with alanine substitutions quantitatively correlated with the degree of αIIbβ3 activation.
The study established a direct link between interaction geometry at mutation-sensitive sites and integrin functional activity.

Conclusions:

Interaction geometry at mutation-sensitive positions is critical for maintaining the stability of the integrin αIIbβ3 heterodimer.
Destabilizing these interactions through alanine substitutions provides a model for constitutive integrin activation.
This research elucidates the structural underpinnings of integrin regulation and protein-protein interaction stability.