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Highly homologous proteins exert opposite biological activities by using different interaction interfaces
We present a possible molecular basis for the opposite activity of two homologues proteins that bind similar ligands and show that this is achieved by fine-tuning of the interaction interface. The highly homologous ASPP proteins have opposite roles in regulating apoptosis: ASPP2 induces apoptosis wh...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486954/ https://www.ncbi.nlm.nih.gov/pubmed/26130271 http://dx.doi.org/10.1038/srep11629 |
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author | Iosub Amir, Anat van Rosmalen, Martijn Mayer, Guy Lebendiker, Mario Danieli, Tsafi Friedler, Assaf |
author_facet | Iosub Amir, Anat van Rosmalen, Martijn Mayer, Guy Lebendiker, Mario Danieli, Tsafi Friedler, Assaf |
author_sort | Iosub Amir, Anat |
collection | PubMed |
description | We present a possible molecular basis for the opposite activity of two homologues proteins that bind similar ligands and show that this is achieved by fine-tuning of the interaction interface. The highly homologous ASPP proteins have opposite roles in regulating apoptosis: ASPP2 induces apoptosis while iASPP inhibits it. The ASPP proteins are regulated by an autoinhibitory interaction between their Ank-SH3 and Pro domains. We performed a detailed biophysical and molecular study of the Pro – Ank-SH3 interaction in iASPP and compared it to the interaction in ASPP2. We found that iASPP Pro is disordered and that the interaction sites are entirely different: iASPP Ank-SH3 binds iASPP Pro via its fourth Ank repeat and RT loop while ASPP2 Ank-SH3 binds ASPP2 Pro via its first Ank repeat and the n-src loop. It is possible that by using different moieties in the same interface, the proteins can have distinct and specific interactions resulting in differential regulation and ultimately different biological activities. |
format | Online Article Text |
id | pubmed-4486954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44869542015-07-08 Highly homologous proteins exert opposite biological activities by using different interaction interfaces Iosub Amir, Anat van Rosmalen, Martijn Mayer, Guy Lebendiker, Mario Danieli, Tsafi Friedler, Assaf Sci Rep Article We present a possible molecular basis for the opposite activity of two homologues proteins that bind similar ligands and show that this is achieved by fine-tuning of the interaction interface. The highly homologous ASPP proteins have opposite roles in regulating apoptosis: ASPP2 induces apoptosis while iASPP inhibits it. The ASPP proteins are regulated by an autoinhibitory interaction between their Ank-SH3 and Pro domains. We performed a detailed biophysical and molecular study of the Pro – Ank-SH3 interaction in iASPP and compared it to the interaction in ASPP2. We found that iASPP Pro is disordered and that the interaction sites are entirely different: iASPP Ank-SH3 binds iASPP Pro via its fourth Ank repeat and RT loop while ASPP2 Ank-SH3 binds ASPP2 Pro via its first Ank repeat and the n-src loop. It is possible that by using different moieties in the same interface, the proteins can have distinct and specific interactions resulting in differential regulation and ultimately different biological activities. Nature Publishing Group 2015-07-01 /pmc/articles/PMC4486954/ /pubmed/26130271 http://dx.doi.org/10.1038/srep11629 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Iosub Amir, Anat van Rosmalen, Martijn Mayer, Guy Lebendiker, Mario Danieli, Tsafi Friedler, Assaf Highly homologous proteins exert opposite biological activities by using different interaction interfaces |
title | Highly homologous proteins exert opposite biological activities by using different interaction interfaces |
title_full | Highly homologous proteins exert opposite biological activities by using different interaction interfaces |
title_fullStr | Highly homologous proteins exert opposite biological activities by using different interaction interfaces |
title_full_unstemmed | Highly homologous proteins exert opposite biological activities by using different interaction interfaces |
title_short | Highly homologous proteins exert opposite biological activities by using different interaction interfaces |
title_sort | highly homologous proteins exert opposite biological activities by using different interaction interfaces |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486954/ https://www.ncbi.nlm.nih.gov/pubmed/26130271 http://dx.doi.org/10.1038/srep11629 |
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