Novel peptide-mediated interactions derived from high-resolution 3-dimensional structures.

Many biological responses to intra- and extracellular stimuli are regulated through complex networks of transient protein interactions where a globular domain in one protein recognizes a linear peptide from another, creating a relatively small contact interface. These peptide stretches are often fou...

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Autores principales:	Amelie Stein, Patrick Aloy
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7f60b3fa30774306aca7d38b0ccacdeb
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spelling	oai:doaj.org-article:7f60b3fa30774306aca7d38b0ccacdeb2021-12-02T19:58:24ZNovel peptide-mediated interactions derived from high-resolution 3-dimensional structures.1553-734X1553-735810.1371/journal.pcbi.1000789https://doaj.org/article/7f60b3fa30774306aca7d38b0ccacdeb2010-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20502673/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Many biological responses to intra- and extracellular stimuli are regulated through complex networks of transient protein interactions where a globular domain in one protein recognizes a linear peptide from another, creating a relatively small contact interface. These peptide stretches are often found in unstructured regions of proteins, and contain a consensus motif complementary to the interaction surface displayed by their binding partners. While most current methods for the de novo discovery of such motifs exploit their tendency to occur in disordered regions, our work here focuses on another observation: upon binding to their partner domain, motifs adopt a well-defined structure. Indeed, through the analysis of all peptide-mediated interactions of known high-resolution three-dimensional (3D) structure, we found that the structure of the peptide may be as characteristic as the consensus motif, and help identify target peptides even though they do not match the established patterns. Our analyses of the structural features of known motifs reveal that they tend to have a particular stretched and elongated structure, unlike most other peptides of the same length. Accordingly, we have implemented a strategy based on a Support Vector Machine that uses this features, along with other structure-encoded information about binding interfaces, to search the set of protein interactions of known 3D structure and to identify unnoticed peptide-mediated interactions among them. We have also derived consensus patterns for these interactions, whenever enough information was available, and compared our results with established linear motif patterns and their binding domains. Finally, to cross-validate our identification strategy, we scanned interactome networks from four model organisms with our newly derived patterns to see if any of them occurred more often than expected. Indeed, we found significant over-representations for 64 domain-motif interactions, 46 of which had not been described before, involving over 6,000 interactions in total for which we could suggest the molecular details determining the binding.Amelie SteinPatrick AloyPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 6, Iss 5, p e1000789 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Amelie Stein Patrick Aloy Novel peptide-mediated interactions derived from high-resolution 3-dimensional structures.
description	Many biological responses to intra- and extracellular stimuli are regulated through complex networks of transient protein interactions where a globular domain in one protein recognizes a linear peptide from another, creating a relatively small contact interface. These peptide stretches are often found in unstructured regions of proteins, and contain a consensus motif complementary to the interaction surface displayed by their binding partners. While most current methods for the de novo discovery of such motifs exploit their tendency to occur in disordered regions, our work here focuses on another observation: upon binding to their partner domain, motifs adopt a well-defined structure. Indeed, through the analysis of all peptide-mediated interactions of known high-resolution three-dimensional (3D) structure, we found that the structure of the peptide may be as characteristic as the consensus motif, and help identify target peptides even though they do not match the established patterns. Our analyses of the structural features of known motifs reveal that they tend to have a particular stretched and elongated structure, unlike most other peptides of the same length. Accordingly, we have implemented a strategy based on a Support Vector Machine that uses this features, along with other structure-encoded information about binding interfaces, to search the set of protein interactions of known 3D structure and to identify unnoticed peptide-mediated interactions among them. We have also derived consensus patterns for these interactions, whenever enough information was available, and compared our results with established linear motif patterns and their binding domains. Finally, to cross-validate our identification strategy, we scanned interactome networks from four model organisms with our newly derived patterns to see if any of them occurred more often than expected. Indeed, we found significant over-representations for 64 domain-motif interactions, 46 of which had not been described before, involving over 6,000 interactions in total for which we could suggest the molecular details determining the binding.
format	article
author	Amelie Stein Patrick Aloy
author_facet	Amelie Stein Patrick Aloy
author_sort	Amelie Stein
title	Novel peptide-mediated interactions derived from high-resolution 3-dimensional structures.
title_short	Novel peptide-mediated interactions derived from high-resolution 3-dimensional structures.
title_full	Novel peptide-mediated interactions derived from high-resolution 3-dimensional structures.
title_fullStr	Novel peptide-mediated interactions derived from high-resolution 3-dimensional structures.
title_full_unstemmed	Novel peptide-mediated interactions derived from high-resolution 3-dimensional structures.
title_sort	novel peptide-mediated interactions derived from high-resolution 3-dimensional structures.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/7f60b3fa30774306aca7d38b0ccacdeb
work_keys_str_mv	AT ameliestein novelpeptidemediatedinteractionsderivedfromhighresolution3dimensionalstructures AT patrickaloy novelpeptidemediatedinteractionsderivedfromhighresolution3dimensionalstructures
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Novel peptide-mediated interactions derived from high-resolution 3-dimensional structures.

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