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Inhibition of Protein Aggregation: Supramolecular Assemblies of Arginine Hold the Key
BACKGROUND: Aggregation of unfolded proteins occurs mainly through the exposed hydrophobic surfaces. Any mechanism of inhibition of this aggregation should explain the prevention of these hydrophobic interactions. Though arginine is prevalently used as an aggregation suppressor, its mechanism of act...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064962/ https://www.ncbi.nlm.nih.gov/pubmed/18000547 http://dx.doi.org/10.1371/journal.pone.0001176 |
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author | Das, Utpal Hariprasad, Gururao Ethayathulla, Abdul S. Manral, Pallavi Das, Taposh K. Pasha, Santosh Mann, Anita Ganguli, Munia Verma, Amit K. Bhat, Rajiv Chandrayan, Sanjeev Kumar Ahmed, Shubbir Sharma, Sujata Kaur, Punit Singh, Tej P. Srinivasan, Alagiri |
author_facet | Das, Utpal Hariprasad, Gururao Ethayathulla, Abdul S. Manral, Pallavi Das, Taposh K. Pasha, Santosh Mann, Anita Ganguli, Munia Verma, Amit K. Bhat, Rajiv Chandrayan, Sanjeev Kumar Ahmed, Shubbir Sharma, Sujata Kaur, Punit Singh, Tej P. Srinivasan, Alagiri |
author_sort | Das, Utpal |
collection | PubMed |
description | BACKGROUND: Aggregation of unfolded proteins occurs mainly through the exposed hydrophobic surfaces. Any mechanism of inhibition of this aggregation should explain the prevention of these hydrophobic interactions. Though arginine is prevalently used as an aggregation suppressor, its mechanism of action is not clearly understood. We propose a mechanism based on the hydrophobic interactions of arginine. METHODOLOGY: We have analyzed arginine solution for its hydrotropic effect by pyrene solubility and the presence of hydrophobic environment by 1-anilino-8-naphthalene sulfonic acid fluorescence. Mass spectroscopic analyses show that arginine forms molecular clusters in the gas phase and the cluster composition is dependent on the solution conditions. Light scattering studies indicate that arginine exists as clusters in solution. In the presence of arginine, the reverse phase chromatographic elution profile of Alzheimer's amyloid beta 1-42 (Aβ(1-42)) peptide is modified. Changes in the hydrodynamic volume of Aβ(1-42) in the presence of arginine measured by size exclusion chromatography show that arginine binds to Aβ(1-42). Arginine increases the solubility of Aβ(1-42) peptide in aqueous medium. It decreases the aggregation of Aβ(1-42) as observed by atomic force microscopy. CONCLUSIONS: Based on our experimental results we propose that molecular clusters of arginine in aqueous solutions display a hydrophobic surface by the alignment of its three methylene groups. The hydrophobic surfaces present on the proteins interact with the hydrophobic surface presented by the arginine clusters. The masking of hydrophobic surface inhibits protein-protein aggregation. This mechanism is also responsible for the hydrotropic effect of arginine on various compounds. It is also explained why other amino acids fail to inhibit the protein aggregation. |
format | Text |
id | pubmed-2064962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-20649622007-11-14 Inhibition of Protein Aggregation: Supramolecular Assemblies of Arginine Hold the Key Das, Utpal Hariprasad, Gururao Ethayathulla, Abdul S. Manral, Pallavi Das, Taposh K. Pasha, Santosh Mann, Anita Ganguli, Munia Verma, Amit K. Bhat, Rajiv Chandrayan, Sanjeev Kumar Ahmed, Shubbir Sharma, Sujata Kaur, Punit Singh, Tej P. Srinivasan, Alagiri PLoS One Research Article BACKGROUND: Aggregation of unfolded proteins occurs mainly through the exposed hydrophobic surfaces. Any mechanism of inhibition of this aggregation should explain the prevention of these hydrophobic interactions. Though arginine is prevalently used as an aggregation suppressor, its mechanism of action is not clearly understood. We propose a mechanism based on the hydrophobic interactions of arginine. METHODOLOGY: We have analyzed arginine solution for its hydrotropic effect by pyrene solubility and the presence of hydrophobic environment by 1-anilino-8-naphthalene sulfonic acid fluorescence. Mass spectroscopic analyses show that arginine forms molecular clusters in the gas phase and the cluster composition is dependent on the solution conditions. Light scattering studies indicate that arginine exists as clusters in solution. In the presence of arginine, the reverse phase chromatographic elution profile of Alzheimer's amyloid beta 1-42 (Aβ(1-42)) peptide is modified. Changes in the hydrodynamic volume of Aβ(1-42) in the presence of arginine measured by size exclusion chromatography show that arginine binds to Aβ(1-42). Arginine increases the solubility of Aβ(1-42) peptide in aqueous medium. It decreases the aggregation of Aβ(1-42) as observed by atomic force microscopy. CONCLUSIONS: Based on our experimental results we propose that molecular clusters of arginine in aqueous solutions display a hydrophobic surface by the alignment of its three methylene groups. The hydrophobic surfaces present on the proteins interact with the hydrophobic surface presented by the arginine clusters. The masking of hydrophobic surface inhibits protein-protein aggregation. This mechanism is also responsible for the hydrotropic effect of arginine on various compounds. It is also explained why other amino acids fail to inhibit the protein aggregation. Public Library of Science 2007-11-14 /pmc/articles/PMC2064962/ /pubmed/18000547 http://dx.doi.org/10.1371/journal.pone.0001176 Text en Das et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Das, Utpal Hariprasad, Gururao Ethayathulla, Abdul S. Manral, Pallavi Das, Taposh K. Pasha, Santosh Mann, Anita Ganguli, Munia Verma, Amit K. Bhat, Rajiv Chandrayan, Sanjeev Kumar Ahmed, Shubbir Sharma, Sujata Kaur, Punit Singh, Tej P. Srinivasan, Alagiri Inhibition of Protein Aggregation: Supramolecular Assemblies of Arginine Hold the Key |
title | Inhibition of Protein Aggregation: Supramolecular Assemblies of Arginine Hold the Key |
title_full | Inhibition of Protein Aggregation: Supramolecular Assemblies of Arginine Hold the Key |
title_fullStr | Inhibition of Protein Aggregation: Supramolecular Assemblies of Arginine Hold the Key |
title_full_unstemmed | Inhibition of Protein Aggregation: Supramolecular Assemblies of Arginine Hold the Key |
title_short | Inhibition of Protein Aggregation: Supramolecular Assemblies of Arginine Hold the Key |
title_sort | inhibition of protein aggregation: supramolecular assemblies of arginine hold the key |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064962/ https://www.ncbi.nlm.nih.gov/pubmed/18000547 http://dx.doi.org/10.1371/journal.pone.0001176 |
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