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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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.
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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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