Abstract

Integrin receptors bind collagen via metal-mediated interactions that are modulated by magnesium (Mg2+) levels in the extracellular matrix. Nuclear magnetic resonance-based relaxation experiments, isothermal titration calorimetry, and adhesion assays reveal that Mg2+ functions as both a structural anchor and dynamic switch of the α1β1 integrin I domain (α1I). Specifically, Mg2+ binding activates micro- to millisecond timescale motions of residues distal to the binding site, particularly those surrounding thesalt bridge at helix 7 and near the metal ion-dependent adhesion site. Mutagenesis of these residues impacts α1I functional activity, thereby suggesting that Mg-bound α1I dynamics are important for collagen binding and consequent allosteric rearrangement of the low-affinity closed to high-affinityopen conformation. We propose a multistep recognition mechanism for α1I-Mg-collagen interactions involving both conformational selection and induced-fit processes. Our findings unravel the multifaceted role of Mg2+ in integrin-collagen recognition and assist in elucidating the molecular mechanisms by which metals regulate protein-protein interactions.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.