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Link to original content: http://pubmed.ncbi.nlm.nih.gov/39298480/
Nanoscale dynamics of the cadherin-catenin complex bound to vinculin revealed by neutron spin echo spectroscopy - PubMed Skip to main page content
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. 2024 Sep 24;121(39):e2408459121.
doi: 10.1073/pnas.2408459121. Epub 2024 Sep 19.

Nanoscale dynamics of the cadherin-catenin complex bound to vinculin revealed by neutron spin echo spectroscopy

David J E Callaway  1 , Iain D Nicholl  2 , Bright Shi  1   3 , Gilbert Reyes  1   3 , Bela Farago  4 , Zimei Bu  1   3
Affiliations

Nanoscale dynamics of the cadherin-catenin complex bound to vinculin revealed by neutron spin echo spectroscopy

David J E Callaway et al. Proc Natl Acad Sci U S A. .

Abstract

We report a neutron spin echo (NSE) study of the nanoscale dynamics of the cell-cell adhesion cadherin-catenin complex bound to vinculin. Our measurements and theoretical physics analyses of the NSE data reveal that the dynamics of full-length α-catenin, β-catenin, and vinculin residing in the cadherin-catenin-vinculin complex become activated, involving nanoscale motions in this complex. The cadherin-catenin complex is the central component of the cell-cell adherens junction (AJ) and is fundamental to embryogenesis, tissue wound healing, neuronal plasticity, cancer metastasis, and cardiovascular health and disease. A highly dynamic cadherin-catenin-vinculin complex provides the molecular dynamics basis for the flexibility and elasticity that are necessary for the AJs to function as force transducers. Our theoretical physics analysis provides a way to elucidate these driving nanoscale motions within the complex without requiring large-scale numerical simulations, providing insights not accessible by other techniques. We propose a three-way "motorman" entropic spring model for the dynamic cadherin-catenin-vinculin complex, which allows the complex to function as a flexible and elastic force transducer.

Keywords: adherens junction; mechanotransduction; nonequilibrium statistical mechanics; protein dynamics; quasielastic neutron scattering.

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Conflict of interest statement

Competing interests statement:The authors declare no competing interest.

Figures

Fig. 1.
Fig. 1.
Protein and domain organization of the VABE complex. (A) Structural model of VABE complex. The all-atomistic model shown represents an ensemble-averaged structure obtained from small-angle neutron and X-ray scattering as we reported previously (44). Also, see SI Appendix, Supplemental Materials 1. Outline of steps to construct VABE structure using small-angle X-ray and neutron scattering data. (B) Primary structure and domain arrangement of α-catenin, β-catenin, and vinculin.
Fig. 2.
Fig. 2.
NSE spectra and Deff(q) of VABE complexes. (Upper) NSE measured I(q,t) / I(q,0) for (A) fully hydrogenated hVhAhBhE, (B) selectively deuterated dVhAdBdE, and (C) hVdAdBdE complexes. (Lower) Deff(q) of (D) hVhAhBhE, (E) dVhAdBdE, (F) hVdAdBdE. The full spectra and initial slope fittings are shown in SI Appendix, Figs. S1–S3.
Fig. 3.
Fig. 3.
Analysis of NSE result—the 3-module model of motion in VABE complex. (A) all proteins in VABE complex are rigid (all gray), (B) β-catenin and vinculin are rigid (gray), but α-catenin is dynamic with motions (green), (C) α-catenin and vinculin are rigid (gray), but β-catenin is dynamic (cyan), (D) α-catenin and β-catenin are rigid (gray) but vinculin is dynamic (magenta), (E) all proteins in VABE are dynamic, moving as independent modules, (F) comparing NSE Deff(q) with those calculated from models (A–E).
Fig. 4.
Fig. 4.
The 4-module model of motion in VABE complex. (A) Motorman trunk and hip are rigid (blue), but two legs (green and magenta) are dynamic. (B) motorman hip and the α-catenin leg are rigid (blue), but the trunk (cyan) and the vinculin leg (magenta) are dynamic. (C) Motorman hip and the vinculin leg are rigid (blue), but the trunk (cyan) and the α-catenin leg (green) are dynamic. (D) All four modules of motorman, trunk (cyan), hip (blue), and two legs (green and magenta) are dynamic. (E) Comparing NSE Deff(q) with those calculated from models (A–D).
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