Disordered binding regions and linear motifs--bridging the gap between two models of molecular recognition.

Intrinsically disordered proteins (IDPs) exist without the presence of a stable tertiary structure in isolation. These proteins are often involved in molecular recognition processes via their disordered binding regions that can recognize partner molecules by undergoing a coupled folding and binding...

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Main Authors: Bálint Mészáros, Zsuzsanna Dosztányi, István Simon
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23056474/pdf/?tool=EBI
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author Bálint Mészáros
Zsuzsanna Dosztányi
István Simon
author_facet Bálint Mészáros
Zsuzsanna Dosztányi
István Simon
author_sort Bálint Mészáros
collection DOAJ
description Intrinsically disordered proteins (IDPs) exist without the presence of a stable tertiary structure in isolation. These proteins are often involved in molecular recognition processes via their disordered binding regions that can recognize partner molecules by undergoing a coupled folding and binding process. The specific properties of disordered binding regions give way to specific, yet transient interactions that enable IDPs to play central roles in signaling pathways and act as hubs of protein interaction networks. An alternative model of protein-protein interactions with largely overlapping functional properties is offered by the concept of linear interaction motifs. This approach focuses on distilling a short consensus sequence pattern from proteins with a common interaction partner. These motifs often reside in disordered regions and are considered to mediate the interaction roughly independent from the rest of the protein. Although a connection between linear motifs and disordered binding regions has been established through common examples, the complementary nature of the two concepts has yet to be fully explored. In many cases the sequence based definition of linear motifs and the structural context based definition of disordered binding regions describe two aspects of the same phenomenon. To gain insight into the connection between the two models, prediction methods were utilized. We combined the regular expression based prediction of linear motifs with the disordered binding region prediction method ANCHOR, each specialized for either model to get the best of both worlds. The thorough analysis of the overlap of the two methods offers a bioinformatics tool for more efficient binding site prediction that can serve a wide range of practical implications. At the same time it can also shed light on the theoretical connection between the two co-existing interaction models.
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spelling doaj.art-876c8045480c4bb59ff80de9245bd8622022-12-21T23:08:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4682910.1371/journal.pone.0046829Disordered binding regions and linear motifs--bridging the gap between two models of molecular recognition.Bálint MészárosZsuzsanna DosztányiIstván SimonIntrinsically disordered proteins (IDPs) exist without the presence of a stable tertiary structure in isolation. These proteins are often involved in molecular recognition processes via their disordered binding regions that can recognize partner molecules by undergoing a coupled folding and binding process. The specific properties of disordered binding regions give way to specific, yet transient interactions that enable IDPs to play central roles in signaling pathways and act as hubs of protein interaction networks. An alternative model of protein-protein interactions with largely overlapping functional properties is offered by the concept of linear interaction motifs. This approach focuses on distilling a short consensus sequence pattern from proteins with a common interaction partner. These motifs often reside in disordered regions and are considered to mediate the interaction roughly independent from the rest of the protein. Although a connection between linear motifs and disordered binding regions has been established through common examples, the complementary nature of the two concepts has yet to be fully explored. In many cases the sequence based definition of linear motifs and the structural context based definition of disordered binding regions describe two aspects of the same phenomenon. To gain insight into the connection between the two models, prediction methods were utilized. We combined the regular expression based prediction of linear motifs with the disordered binding region prediction method ANCHOR, each specialized for either model to get the best of both worlds. The thorough analysis of the overlap of the two methods offers a bioinformatics tool for more efficient binding site prediction that can serve a wide range of practical implications. At the same time it can also shed light on the theoretical connection between the two co-existing interaction models.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23056474/pdf/?tool=EBI
spellingShingle Bálint Mészáros
Zsuzsanna Dosztányi
István Simon
Disordered binding regions and linear motifs--bridging the gap between two models of molecular recognition.
PLoS ONE
title Disordered binding regions and linear motifs--bridging the gap between two models of molecular recognition.
title_full Disordered binding regions and linear motifs--bridging the gap between two models of molecular recognition.
title_fullStr Disordered binding regions and linear motifs--bridging the gap between two models of molecular recognition.
title_full_unstemmed Disordered binding regions and linear motifs--bridging the gap between two models of molecular recognition.
title_short Disordered binding regions and linear motifs--bridging the gap between two models of molecular recognition.
title_sort disordered binding regions and linear motifs bridging the gap between two models of molecular recognition
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23056474/pdf/?tool=EBI
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