51. Fuzzy binding model of molecular interactions between tropoelastin and integrin alphaVbeta3.
- Author
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Ozsvar J, Wang R, Tarakanova A, Buehler MJ, and Weiss AS
- Subjects
- Binding Sites, Elastin, Extracellular Matrix, Humans, Integrin alphaVbeta3, Tropoelastin
- Abstract
Tropoelastin is the highly flexible monomer subunit of elastin, required for the resilience of the extracellular matrix in elastic tissues. To elicit biological signaling, multiple sites on tropoelastin bind to cell surface integrins in a poorly understood multifactorial process. We constructed a full atomistic molecular model of the interactions between tropoelastin and integrin α
v β3 using ensemble-based computational methodologies. Conformational changes of integrin αv β3 associated with outside-in signaling were more frequently facilitated in an ensemble in which tropoelastin bound the integrin's α1 helix rather than the upstream canonical binding site. Our findings support a model of fuzzy binding, whereby many tropoelastin conformations and defined sites cooperatively interact with multiple αv β3 regions. This model explains prior experimental binding to distinct tropoelastin regions, domains 17 and 36, and points to the cooperative participation of domain 20. Our study highlights the utility of ensemble-based approaches in helping to understand the interactive mechanisms of functionally significant flexible proteins., (Copyright © 2021 Biophysical Society. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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