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Key Interactions in Integrin Ectodomain Responsible for Global Conformational Change Detected by Elastic Network Normal-Mode Analysis
Integrin, a membrane protein with a huge extracellular domain, participates in cell-cell and cell-extracellular-matrix interactions for metazoan. A group of integrins is known to perform a large-scale structural change when the protein is activated, but the activation mechanism and generality of the...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Biophysical Society
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527288/ https://www.ncbi.nlm.nih.gov/pubmed/18515366 http://dx.doi.org/10.1529/biophysj.108.131045 |
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author | Matsumoto, Atsushi Kamata, Tetsuji Takagi, Junichi Iwasaki, Kenji Yura, Kei |
author_facet | Matsumoto, Atsushi Kamata, Tetsuji Takagi, Junichi Iwasaki, Kenji Yura, Kei |
author_sort | Matsumoto, Atsushi |
collection | PubMed |
description | Integrin, a membrane protein with a huge extracellular domain, participates in cell-cell and cell-extracellular-matrix interactions for metazoan. A group of integrins is known to perform a large-scale structural change when the protein is activated, but the activation mechanism and generality of the conformational change remain to be elucidated. We performed normal-mode analysis of the elastic network model on integrin α(V)β(3) ectodomain in the bent form and identified key residues that influenced molecular motions. Iterative normal-mode calculations demonstrated that the specific nonbonded interactions involving the key residues work as a snap to keep integrin in the bent form. The importance of the key residues for the conformational change was further verified by mutation experiments, in which integrin α(IIb)β(3) was used. The conservation pattern of amino acid residues among the integrin family showed that the characteristic pattern of residues seen around these key residues is found in the limited groups of integrin β-chains. This conservation pattern suggests that the molecular mechanism of the conformational change relying on the interactions found in integrin α(V)β(3) is unique to the limited types of integrins. |
format | Text |
id | pubmed-2527288 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Biophysical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-25272882008-09-26 Key Interactions in Integrin Ectodomain Responsible for Global Conformational Change Detected by Elastic Network Normal-Mode Analysis Matsumoto, Atsushi Kamata, Tetsuji Takagi, Junichi Iwasaki, Kenji Yura, Kei Biophys J Proteins Integrin, a membrane protein with a huge extracellular domain, participates in cell-cell and cell-extracellular-matrix interactions for metazoan. A group of integrins is known to perform a large-scale structural change when the protein is activated, but the activation mechanism and generality of the conformational change remain to be elucidated. We performed normal-mode analysis of the elastic network model on integrin α(V)β(3) ectodomain in the bent form and identified key residues that influenced molecular motions. Iterative normal-mode calculations demonstrated that the specific nonbonded interactions involving the key residues work as a snap to keep integrin in the bent form. The importance of the key residues for the conformational change was further verified by mutation experiments, in which integrin α(IIb)β(3) was used. The conservation pattern of amino acid residues among the integrin family showed that the characteristic pattern of residues seen around these key residues is found in the limited groups of integrin β-chains. This conservation pattern suggests that the molecular mechanism of the conformational change relying on the interactions found in integrin α(V)β(3) is unique to the limited types of integrins. The Biophysical Society 2008-09-15 2008-05-30 /pmc/articles/PMC2527288/ /pubmed/18515366 http://dx.doi.org/10.1529/biophysj.108.131045 Text en Copyright © 2008, Biophysical Society This is an Open Access article distributed under the terms of the Creative Commons-Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/2.0/), which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Proteins Matsumoto, Atsushi Kamata, Tetsuji Takagi, Junichi Iwasaki, Kenji Yura, Kei Key Interactions in Integrin Ectodomain Responsible for Global Conformational Change Detected by Elastic Network Normal-Mode Analysis |
title | Key Interactions in Integrin Ectodomain Responsible for Global Conformational Change Detected by Elastic Network Normal-Mode Analysis |
title_full | Key Interactions in Integrin Ectodomain Responsible for Global Conformational Change Detected by Elastic Network Normal-Mode Analysis |
title_fullStr | Key Interactions in Integrin Ectodomain Responsible for Global Conformational Change Detected by Elastic Network Normal-Mode Analysis |
title_full_unstemmed | Key Interactions in Integrin Ectodomain Responsible for Global Conformational Change Detected by Elastic Network Normal-Mode Analysis |
title_short | Key Interactions in Integrin Ectodomain Responsible for Global Conformational Change Detected by Elastic Network Normal-Mode Analysis |
title_sort | key interactions in integrin ectodomain responsible for global conformational change detected by elastic network normal-mode analysis |
topic | Proteins |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527288/ https://www.ncbi.nlm.nih.gov/pubmed/18515366 http://dx.doi.org/10.1529/biophysj.108.131045 |
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