Structural and functional roles of coevolved sites in proteins.

Understanding the residue covariations between multiple positions in protein families is very crucial and can be helpful for designing protein engineering experiments. These simultaneous changes or residue coevolution allow protein to maintain its overall structural-functional integrity while enabli...

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Main Authors: Saikat Chakrabarti, Anna R Panchenko
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2797611?pdf=render
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spelling doaj-e86f702cba90404891136009b61b6ca12020-11-24T22:06:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0151e859110.1371/journal.pone.0008591Structural and functional roles of coevolved sites in proteins.Saikat ChakrabartiAnna R PanchenkoUnderstanding the residue covariations between multiple positions in protein families is very crucial and can be helpful for designing protein engineering experiments. These simultaneous changes or residue coevolution allow protein to maintain its overall structural-functional integrity while enabling it to acquire specific functional modifications. Despite the significant efforts in the field there is still controversy in terms of the preferable locations of coevolved residues on different regions of protein molecules, the strength of coevolutionary signal and role of coevolution in functional diversification.In this paper we study the scale and nature of residue coevolution in maintaining the overall functionality and structural integrity of proteins. We employed a large scale study to investigate the structural and functional aspects of coevolved residues. We found that the networks representing the coevolutionary residue connections within our dataset are in general of 'small-world' type as they have clustering coefficient values higher than random networks and also show smaller mean shortest path lengths similar and/or lower than random and regular networks. We also found that altogether 11% of functionally important sites are coevolved with any other sites. Active sites are found more frequently to coevolve with any other sites (15%) compared to protein (11%) and ligand (9%) binding sites. Metal binding and active sites are also found to be more frequently coevolved with other metal binding and active sites, respectively. Analysis of the coupling between coevolutionary processes and the spatial distribution of coevolved sites reveals that a high fraction of coevolved sites are located close to each other. Moreover, approximately 80% of charge compensatory substitutions within coevolved sites are found at very close spatial proximity (<or= 5A), pointing to the possible preservation of salt bridges in evolution.Our findings show that a noticeable fraction of functionally important sites undergo coevolution and also point towards compensatory substitutions as a probable coevolutionary mechanism within spatially proximal coevolved functional sites.http://europepmc.org/articles/PMC2797611?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Saikat Chakrabarti
Anna R Panchenko
spellingShingle Saikat Chakrabarti
Anna R Panchenko
Structural and functional roles of coevolved sites in proteins.
PLoS ONE
author_facet Saikat Chakrabarti
Anna R Panchenko
author_sort Saikat Chakrabarti
title Structural and functional roles of coevolved sites in proteins.
title_short Structural and functional roles of coevolved sites in proteins.
title_full Structural and functional roles of coevolved sites in proteins.
title_fullStr Structural and functional roles of coevolved sites in proteins.
title_full_unstemmed Structural and functional roles of coevolved sites in proteins.
title_sort structural and functional roles of coevolved sites in proteins.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2010-01-01
description Understanding the residue covariations between multiple positions in protein families is very crucial and can be helpful for designing protein engineering experiments. These simultaneous changes or residue coevolution allow protein to maintain its overall structural-functional integrity while enabling it to acquire specific functional modifications. Despite the significant efforts in the field there is still controversy in terms of the preferable locations of coevolved residues on different regions of protein molecules, the strength of coevolutionary signal and role of coevolution in functional diversification.In this paper we study the scale and nature of residue coevolution in maintaining the overall functionality and structural integrity of proteins. We employed a large scale study to investigate the structural and functional aspects of coevolved residues. We found that the networks representing the coevolutionary residue connections within our dataset are in general of 'small-world' type as they have clustering coefficient values higher than random networks and also show smaller mean shortest path lengths similar and/or lower than random and regular networks. We also found that altogether 11% of functionally important sites are coevolved with any other sites. Active sites are found more frequently to coevolve with any other sites (15%) compared to protein (11%) and ligand (9%) binding sites. Metal binding and active sites are also found to be more frequently coevolved with other metal binding and active sites, respectively. Analysis of the coupling between coevolutionary processes and the spatial distribution of coevolved sites reveals that a high fraction of coevolved sites are located close to each other. Moreover, approximately 80% of charge compensatory substitutions within coevolved sites are found at very close spatial proximity (<or= 5A), pointing to the possible preservation of salt bridges in evolution.Our findings show that a noticeable fraction of functionally important sites undergo coevolution and also point towards compensatory substitutions as a probable coevolutionary mechanism within spatially proximal coevolved functional sites.
url http://europepmc.org/articles/PMC2797611?pdf=render
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