Interaction Analyses of the Integrin β2 Cytoplasmic Tail with the F3 FERM Domain of Talin and 14-3-3ζ Reveal a Ternary Complex with Phosphorylated Tail

Integrins, which are heterodimeric (α and β subunits) signal-transducer proteins, are essential for cell adhesion and migration. β cytosolic tails (β-CTs) of integrins interact with a number of cytosolic proteins including talin, Dok1, and 14-3-3ζ. The formation of multiprotein complexes with β-CTs...

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Main Authors: Chatterjee, Deepak, Lu, Lewis Zhiping, Tan, Suet-Mien, Bhattacharjya, Surajit
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2017
Subjects:
NMR
Online Access:https://hdl.handle.net/10356/85152
http://hdl.handle.net/10220/43654
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-851522023-02-28T16:59:59Z Interaction Analyses of the Integrin β2 Cytoplasmic Tail with the F3 FERM Domain of Talin and 14-3-3ζ Reveal a Ternary Complex with Phosphorylated Tail Chatterjee, Deepak Lu, Lewis Zhiping Tan, Suet-Mien Bhattacharjya, Surajit School of Biological Sciences β2 integrins NMR Integrins, which are heterodimeric (α and β subunits) signal-transducer proteins, are essential for cell adhesion and migration. β cytosolic tails (β-CTs) of integrins interact with a number of cytosolic proteins including talin, Dok1, and 14-3-3ζ. The formation of multiprotein complexes with β-CTs is involved in the activation and regulation of integrins. The leukocyte-specific β2 integrins are essential for leukocyte trafficking, phagocytosis, antigen presentation, and proliferation. In this study, we examined the binding interactions between integrin β2-CT and T758-phosphorylated β2-CT with positive regulators talin and 14-3-3ζ and negative regulator Dok1. Residues of the F3 domain of talin belonging to the C-terminal helix, β-strand 5, and the adjacent loop were found to be involved in the binding interactions with β2-CT. The binding affinity between talin F3 and β2-CT was reduced when β2 T758 was phosphorylated, but this modification promoted 14-3-3ζ binding. However, we were able to detect stable ternary complex formation of T758-phosphorylated β2-CT, talin F3, and 14-3-3ζ that involved the repositioning of talin F3 on β2-CT. We showed that Dok1 binding to β2-CT was reduced in the presence of 14-3-3ζ and when β2 T758 was phosphorylated. Based on these data, we propose a sequential model of β2 integrin activation involving these molecules. Our study provides for the first time insights toward β2 integrin activation that involves a multiprotein complex. MOE (Min. of Education, S’pore) Accepted version 2017-08-30T09:09:53Z 2019-12-06T15:58:13Z 2017-08-30T09:09:53Z 2019-12-06T15:58:13Z 2016 Journal Article Chatterjee, D., Lu, L. Z., Tan, S.-M., & Bhattacharjya, S. (2016). Interaction Analyses of the Integrin β2 Cytoplasmic Tail with the F3 FERM Domain of Talin and 14-3-3ζ Reveal a Ternary Complex with Phosphorylated Tail. Journal of Molecular Biology, 428(20), 4129-4142. 0022-2836 https://hdl.handle.net/10356/85152 http://hdl.handle.net/10220/43654 10.1016/j.jmb.2016.08.014 en Journal of Molecular Biology © 2016 Elsevier Ltd. This is the author created version of a work that has been peer reviewed and accepted for publication by Journal of Molecular Biology, Elsevier. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.jmb.2016.08.014]. 46 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic β2 integrins
NMR
spellingShingle β2 integrins
NMR
Chatterjee, Deepak
Lu, Lewis Zhiping
Tan, Suet-Mien
Bhattacharjya, Surajit
Interaction Analyses of the Integrin β2 Cytoplasmic Tail with the F3 FERM Domain of Talin and 14-3-3ζ Reveal a Ternary Complex with Phosphorylated Tail
description Integrins, which are heterodimeric (α and β subunits) signal-transducer proteins, are essential for cell adhesion and migration. β cytosolic tails (β-CTs) of integrins interact with a number of cytosolic proteins including talin, Dok1, and 14-3-3ζ. The formation of multiprotein complexes with β-CTs is involved in the activation and regulation of integrins. The leukocyte-specific β2 integrins are essential for leukocyte trafficking, phagocytosis, antigen presentation, and proliferation. In this study, we examined the binding interactions between integrin β2-CT and T758-phosphorylated β2-CT with positive regulators talin and 14-3-3ζ and negative regulator Dok1. Residues of the F3 domain of talin belonging to the C-terminal helix, β-strand 5, and the adjacent loop were found to be involved in the binding interactions with β2-CT. The binding affinity between talin F3 and β2-CT was reduced when β2 T758 was phosphorylated, but this modification promoted 14-3-3ζ binding. However, we were able to detect stable ternary complex formation of T758-phosphorylated β2-CT, talin F3, and 14-3-3ζ that involved the repositioning of talin F3 on β2-CT. We showed that Dok1 binding to β2-CT was reduced in the presence of 14-3-3ζ and when β2 T758 was phosphorylated. Based on these data, we propose a sequential model of β2 integrin activation involving these molecules. Our study provides for the first time insights toward β2 integrin activation that involves a multiprotein complex.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Chatterjee, Deepak
Lu, Lewis Zhiping
Tan, Suet-Mien
Bhattacharjya, Surajit
format Article
author Chatterjee, Deepak
Lu, Lewis Zhiping
Tan, Suet-Mien
Bhattacharjya, Surajit
author_sort Chatterjee, Deepak
title Interaction Analyses of the Integrin β2 Cytoplasmic Tail with the F3 FERM Domain of Talin and 14-3-3ζ Reveal a Ternary Complex with Phosphorylated Tail
title_short Interaction Analyses of the Integrin β2 Cytoplasmic Tail with the F3 FERM Domain of Talin and 14-3-3ζ Reveal a Ternary Complex with Phosphorylated Tail
title_full Interaction Analyses of the Integrin β2 Cytoplasmic Tail with the F3 FERM Domain of Talin and 14-3-3ζ Reveal a Ternary Complex with Phosphorylated Tail
title_fullStr Interaction Analyses of the Integrin β2 Cytoplasmic Tail with the F3 FERM Domain of Talin and 14-3-3ζ Reveal a Ternary Complex with Phosphorylated Tail
title_full_unstemmed Interaction Analyses of the Integrin β2 Cytoplasmic Tail with the F3 FERM Domain of Talin and 14-3-3ζ Reveal a Ternary Complex with Phosphorylated Tail
title_sort interaction analyses of the integrin β2 cytoplasmic tail with the f3 ferm domain of talin and 14-3-3ζ reveal a ternary complex with phosphorylated tail
publishDate 2017
url https://hdl.handle.net/10356/85152
http://hdl.handle.net/10220/43654
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