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

• 成果类型: Article
• 署名作者: Callaway, David J. E.; Nicholl, Iain D.; Shi, Bright; Reyes, Gilbert; Farago, Bela; Bu, Zimei
• 署名单位: City University of New York (CUNY) System; City College of New York (CUNY); University of Wolverhampton; City University of New York (CUNY) System; Institut Laue-Langevin (ILL)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8579
• DOI: 10.1073/pnas.2408459121
• 发表日期: 2024-09-24
• 关键词: protein domain motion; alpha-catenin; adherens junctions; actin-binding; cell-adhesion; f-actin; tension; activation; mechanisms; molecule

摘要

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 c- catenin, f3- 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.