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Control of Collagen Stability and Heterotrimer Specificity through Repulsive Electrostatic Interactions

Charge-pair interactions between acidic and basic residues on the surface of collagen can promote stability as well as control specificity of molecular recognition. Heterotrimeric collagen peptides have been engineered de novo using either rational or computational methods, which in both cases optim...

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Detalles Bibliográficos
Autores principales: Parmar, Avanish S., Joshi, Mihir, Nosker, Patrick L., Hasan, Nida F., Nanda, Vikas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030969/
https://www.ncbi.nlm.nih.gov/pubmed/24970200
http://dx.doi.org/10.3390/biom3040986
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author Parmar, Avanish S.
Joshi, Mihir
Nosker, Patrick L.
Hasan, Nida F.
Nanda, Vikas
author_facet Parmar, Avanish S.
Joshi, Mihir
Nosker, Patrick L.
Hasan, Nida F.
Nanda, Vikas
author_sort Parmar, Avanish S.
collection PubMed
description Charge-pair interactions between acidic and basic residues on the surface of collagen can promote stability as well as control specificity of molecular recognition. Heterotrimeric collagen peptides have been engineered de novo using either rational or computational methods, which in both cases optimize networks of favorable charge-pair interactions in the target structure. Less understood is the role of electrostatic repulsion between groups of like charge in destabilizing structure or directing molecular recognition. To study this, we apply a “charge crowding” approach, where repulsive interactions between multiple aspartate side chains are found to destabilize the homotrimer states in triple helical peptide system and can be utilized to promote the formation of heterotrimers. Neutralizing surface charge by increasing salt concentration or decreasing pH can enhance homotrimer stability, confirming the role of charge crowding on the destabilization of homotrimers via electrostatic repulsion. Charge crowding may be used in conjunction with other approaches to create specific collagen heterotrimers.
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spelling pubmed-40309692014-06-24 Control of Collagen Stability and Heterotrimer Specificity through Repulsive Electrostatic Interactions Parmar, Avanish S. Joshi, Mihir Nosker, Patrick L. Hasan, Nida F. Nanda, Vikas Biomolecules Article Charge-pair interactions between acidic and basic residues on the surface of collagen can promote stability as well as control specificity of molecular recognition. Heterotrimeric collagen peptides have been engineered de novo using either rational or computational methods, which in both cases optimize networks of favorable charge-pair interactions in the target structure. Less understood is the role of electrostatic repulsion between groups of like charge in destabilizing structure or directing molecular recognition. To study this, we apply a “charge crowding” approach, where repulsive interactions between multiple aspartate side chains are found to destabilize the homotrimer states in triple helical peptide system and can be utilized to promote the formation of heterotrimers. Neutralizing surface charge by increasing salt concentration or decreasing pH can enhance homotrimer stability, confirming the role of charge crowding on the destabilization of homotrimers via electrostatic repulsion. Charge crowding may be used in conjunction with other approaches to create specific collagen heterotrimers. MDPI 2013-12-05 /pmc/articles/PMC4030969/ /pubmed/24970200 http://dx.doi.org/10.3390/biom3040986 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Parmar, Avanish S.
Joshi, Mihir
Nosker, Patrick L.
Hasan, Nida F.
Nanda, Vikas
Control of Collagen Stability and Heterotrimer Specificity through Repulsive Electrostatic Interactions
title Control of Collagen Stability and Heterotrimer Specificity through Repulsive Electrostatic Interactions
title_full Control of Collagen Stability and Heterotrimer Specificity through Repulsive Electrostatic Interactions
title_fullStr Control of Collagen Stability and Heterotrimer Specificity through Repulsive Electrostatic Interactions
title_full_unstemmed Control of Collagen Stability and Heterotrimer Specificity through Repulsive Electrostatic Interactions
title_short Control of Collagen Stability and Heterotrimer Specificity through Repulsive Electrostatic Interactions
title_sort control of collagen stability and heterotrimer specificity through repulsive electrostatic interactions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030969/
https://www.ncbi.nlm.nih.gov/pubmed/24970200
http://dx.doi.org/10.3390/biom3040986
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