Allosteric Disulfide Bridges in Integrins: The Molecular Switches of Redox Regulation of Integrin-Mediated Cell Functions
Abstract
1. Introduction
2. Not All Cysteine Pairs in Proteins Are Equal
3. Adhesion of Platelets and Cells Are Mediated by Members of the Cysteine-Rich Integrin Receptor Family
4. Structure; Domains and Disulfide Pattern of Integrins
5. The Machinery That Modifies Integrins on the Cell Surface and Redox-Regulates Platelet Adhesion and Deadhesion
6. The Allosteric Disulfide Bridges of Integrins and Their Location
Disulfide Bond | Domain Localization | Homologous Sites in Other Integrins | αC–αC Distance [nm] | Disulfide Strain Energy [kJ/mol] a | Solvent Accessibility [Å2] a | Stereochemical Conformation | Redox-Modifying Enzyme (and Effect) | References |
---|---|---|---|---|---|---|---|---|
C490–C545 | αIIB thigh | C654–C711 in αM | 0.42 | 19.2 | 6.59 | -RH staple | ERp72 on integrin αMβ2 on neutrophils (promoting adhesion) | [25,119] |
C602–C608 | αIIB hinge | C589–C594 in α4 C606–C611 in murine α7 (X2 splice variant) | 0.41 | 9.1 | 2.2 | -LH hook | Reductive cleavage in α4 and disulfide bond formation in α7 promote ligand binding | [112,120,121] |
C177–C184 | β3 A | C169–C176 in β2 A | 0.56 | 17.7 | 0.17 | -/+RH hook | ERp5 (attenuating; reduction of disulfide bond under tension) | [108] |
C232–C273 | β3 A | C224–C264 in β2 A | 0.52 | 10.0 | 8.56 | -RH hook | PDI (attenuating binding affinity) | [118] |
C13–C435 | Interdomain β3 PSI-β3 EGF1 | 0.66 | 15.7 | 1.70 | +/-LH spiral | unknown | ||
C473–C503 | Hinge between EGF1 and EGF2 | 0.68 | 48.4 | 27.37 | -/+RH hook | ERp46 (reductive cleavage, activating integrin) | [109] | |
C437–C457 | EGF1 of β3 | C494–C526 in β7 | 0.54 | 17.2 | 19.90 | -/+RH hook | in αVβ3 and in α4β7 (in the latter, reductive cleavage activates integrin) | [88,90,121,122] |
C523–C544 | EGF3 of β3 (at interface with EGF2) | 0.41 | 17.3 | 3.36 | -LH hook | Putatively ERp57 (inhibiting αIIbβ3, but not αVβ3) | [88,90,122] |
7. The Formation and Cleavage of Allosteric Disulfide Bonds in Integrins Causes Conformational Changes
8. From Disulfide Bridge-Induced Conformational Changes to Cellular Consequences of Integrin-ECM Contacts
9. Concluding Remarks and Future Perspectives
Funding
Acknowledgments
Conflicts of Interest
References
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Eble, J.A. Allosteric Disulfide Bridges in Integrins: The Molecular Switches of Redox Regulation of Integrin-Mediated Cell Functions. Antioxidants 2025, 14, 1005. https://doi.org/10.3390/antiox14081005
Eble JA. Allosteric Disulfide Bridges in Integrins: The Molecular Switches of Redox Regulation of Integrin-Mediated Cell Functions. Antioxidants. 2025; 14(8):1005. https://doi.org/10.3390/antiox14081005
Chicago/Turabian StyleEble, Johannes A. 2025. "Allosteric Disulfide Bridges in Integrins: The Molecular Switches of Redox Regulation of Integrin-Mediated Cell Functions" Antioxidants 14, no. 8: 1005. https://doi.org/10.3390/antiox14081005
APA StyleEble, J. A. (2025). Allosteric Disulfide Bridges in Integrins: The Molecular Switches of Redox Regulation of Integrin-Mediated Cell Functions. Antioxidants, 14(8), 1005. https://doi.org/10.3390/antiox14081005