气候变化领域集成服务门户(CCPortal): Activated nanoscale actin-binding domain motion in the catenin–cadherin complex revealed by neutron spin echo spectroscopy

CCPortal

DOI	10.1073/pnas.2025012118
	Activated nanoscale actin-binding domain motion in the catenin–cadherin complex revealed by neutron spin echo spectroscopy
	Farago B.; Nicholl I.D.; Wang S.; Cheng X.; Callaway D.J.E.; Bu Z.
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	As the core component of the adherens junction in cell–cell adhesion, the cadherin–catenin complex transduces mechanical tension between neighboring cells. Structural studies have shown that the cadherin–catenin complex exists as an ensemble of flexible conformations, with the actin-binding domain (ABD) of α-catenin adopting a variety of configurations. Here, we have determined the nanoscale protein domain dynamics of the cadherin–catenin complex using neutron spin echo spectroscopy (NSE), selective deuteration, and theoretical physics analyses. NSE reveals that, in the cadherin–catenin complex, the motion of the entire ABD becomes activated on nanosecond to submicrosecond timescales. By contrast, in the α-catenin homodimer, only the smaller disordered C-terminal tail of ABD is moving. Molecular dynamics (MD) simulations also show increased mobility of ABD in the cadherin–catenin complex, compared to the α-catenin homodimer. Biased MD simulations further reveal that the applied external forces promote the transition of ABD in the cadherin–catenin complex from an ensemble of diverse conformational states to specific states that resemble the actin-bound structure. The activated motion and an ensemble of flexible configurations of the mechanosensory ABD suggest the formation of an entropic trap in the cadherin–catenin complex, serving as negative allosteric regulation that impedes the complex from binding to actin under zero force. Mechanical tension facilitates the reduction in dynamics and narrows the conformational ensemble of ABD to specific configurations that are well suited to bind F-actin. Our results provide a protein dynamics and entropic explanation for the observed force-sensitive binding behavior of a mechanosensitive protein complex. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Catch bond; Cell adhesion; Mechanotransduction; Neutron spin echo spectroscopy; Protein dynamics
语种	英语
scopus关键词	actin binding protein; alpha catenin; cadherin; catenin; F actin; actin filament; Article; binding affinity; calculation; entropy; mathematical analysis; microfilament; molecular dynamics; neutron scattering; neutron spin echo spectroscopy; principal component analysis; priority journal; probability; protein binding; protein structure; spectroscopy; X ray crystallography
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180107
作者单位	Spectroscopy Group, Institut Laue-Langevin, Grenoble Cedex 9, 38042, France; Department of Biomedical Science and Physiology, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, WV1 1LY, United Kingdom; Division of Medicinal Chemistry and Pharmacognocy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States; Translational Data Analytics Institute, The Ohio State University, Columbus, OH 43210, United States; Department of Chemistry and Biochemistry, City College of New York, City University of New York, New York, NY 10031, United States; PhD Programs in Chemistry and Biochemistry, City University of New York Graduate Center, New York, NY 10016, United States
推荐引用方式 GB/T 7714	Farago B.,Nicholl I.D.,Wang S.,等. Activated nanoscale actin-binding domain motion in the catenin–cadherin complex revealed by neutron spin echo spectroscopy[J],2021,118(13).
APA	Farago B.,Nicholl I.D.,Wang S.,Cheng X.,Callaway D.J.E.,&Bu Z..(2021).Activated nanoscale actin-binding domain motion in the catenin–cadherin complex revealed by neutron spin echo spectroscopy.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	Farago B.,et al."Activated nanoscale actin-binding domain motion in the catenin–cadherin complex revealed by neutron spin echo spectroscopy".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).