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Effects of point mutations in the binding pocket of the mouse major urinary protein MUP20 on ligand affinity and specificity
The mouse Major Urinary Proteins (MUPs) contain a conserved β-barrel structure with a characteristic central hydrophobic pocket that binds a variety of volatile compounds. After release of urine, these molecules are slowly emitted in the environment where they play an important role in chemical comm...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342991/ https://www.ncbi.nlm.nih.gov/pubmed/30670733 http://dx.doi.org/10.1038/s41598-018-36391-3 |
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author | Ricatti, Jimena Acquasaliente, Laura Ribaudo, Giovanni De Filippis, Vincenzo Bellini, Marino Llovera, Ramiro Esteban Barollo, Susi Pezzani, Raffaele Zagotto, Giuseppe Persaud, Krishna C. Mucignat-Caretta, Carla |
author_facet | Ricatti, Jimena Acquasaliente, Laura Ribaudo, Giovanni De Filippis, Vincenzo Bellini, Marino Llovera, Ramiro Esteban Barollo, Susi Pezzani, Raffaele Zagotto, Giuseppe Persaud, Krishna C. Mucignat-Caretta, Carla |
author_sort | Ricatti, Jimena |
collection | PubMed |
description | The mouse Major Urinary Proteins (MUPs) contain a conserved β-barrel structure with a characteristic central hydrophobic pocket that binds a variety of volatile compounds. After release of urine, these molecules are slowly emitted in the environment where they play an important role in chemical communication. MUPs are highly polymorphic and conformationally stable. They may be of interest in the construction of biosensor arrays capable of detection of a broad range of analytes. In this work, 14 critical amino acids in the binding pocket involved in ligand interactions were identified in MUP20 using in silico techniques and 7 MUP20 mutants were synthesised and characterised to produce a set of proteins with diverse ligand binding profiles to structurally different ligands. A single amino acid substitution in the binding pocket can dramatically change the MUPs binding affinity and ligand specificity. These results have great potential for the design of new biosensor and gas-sensor recognition elements. |
format | Online Article Text |
id | pubmed-6342991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63429912019-01-26 Effects of point mutations in the binding pocket of the mouse major urinary protein MUP20 on ligand affinity and specificity Ricatti, Jimena Acquasaliente, Laura Ribaudo, Giovanni De Filippis, Vincenzo Bellini, Marino Llovera, Ramiro Esteban Barollo, Susi Pezzani, Raffaele Zagotto, Giuseppe Persaud, Krishna C. Mucignat-Caretta, Carla Sci Rep Article The mouse Major Urinary Proteins (MUPs) contain a conserved β-barrel structure with a characteristic central hydrophobic pocket that binds a variety of volatile compounds. After release of urine, these molecules are slowly emitted in the environment where they play an important role in chemical communication. MUPs are highly polymorphic and conformationally stable. They may be of interest in the construction of biosensor arrays capable of detection of a broad range of analytes. In this work, 14 critical amino acids in the binding pocket involved in ligand interactions were identified in MUP20 using in silico techniques and 7 MUP20 mutants were synthesised and characterised to produce a set of proteins with diverse ligand binding profiles to structurally different ligands. A single amino acid substitution in the binding pocket can dramatically change the MUPs binding affinity and ligand specificity. These results have great potential for the design of new biosensor and gas-sensor recognition elements. Nature Publishing Group UK 2019-01-22 /pmc/articles/PMC6342991/ /pubmed/30670733 http://dx.doi.org/10.1038/s41598-018-36391-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ricatti, Jimena Acquasaliente, Laura Ribaudo, Giovanni De Filippis, Vincenzo Bellini, Marino Llovera, Ramiro Esteban Barollo, Susi Pezzani, Raffaele Zagotto, Giuseppe Persaud, Krishna C. Mucignat-Caretta, Carla Effects of point mutations in the binding pocket of the mouse major urinary protein MUP20 on ligand affinity and specificity |
title | Effects of point mutations in the binding pocket of the mouse major urinary protein MUP20 on ligand affinity and specificity |
title_full | Effects of point mutations in the binding pocket of the mouse major urinary protein MUP20 on ligand affinity and specificity |
title_fullStr | Effects of point mutations in the binding pocket of the mouse major urinary protein MUP20 on ligand affinity and specificity |
title_full_unstemmed | Effects of point mutations in the binding pocket of the mouse major urinary protein MUP20 on ligand affinity and specificity |
title_short | Effects of point mutations in the binding pocket of the mouse major urinary protein MUP20 on ligand affinity and specificity |
title_sort | effects of point mutations in the binding pocket of the mouse major urinary protein mup20 on ligand affinity and specificity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342991/ https://www.ncbi.nlm.nih.gov/pubmed/30670733 http://dx.doi.org/10.1038/s41598-018-36391-3 |
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