Interface-resolved network of protein-protein interactions.

We define an interface-interaction network (IIN) to capture the specificity and competition between protein-protein interactions (PPI). This new type of network represents interactions between individual interfaces used in functional protein binding and thereby contains the detail necessary to descr...

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Autores principales:	Margaret E Johnson, Gerhard Hummer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/731b2839896f4570974294bc57cc90e3
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spelling	oai:doaj.org-article:731b2839896f4570974294bc57cc90e32021-11-18T05:52:09ZInterface-resolved network of protein-protein interactions.1553-734X1553-735810.1371/journal.pcbi.1003065https://doaj.org/article/731b2839896f4570974294bc57cc90e32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23696724/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358We define an interface-interaction network (IIN) to capture the specificity and competition between protein-protein interactions (PPI). This new type of network represents interactions between individual interfaces used in functional protein binding and thereby contains the detail necessary to describe the competition and cooperation between any pair of binding partners. Here we establish a general framework for the construction of IINs that merges computational structure-based interface assignment with careful curation of available literature. To complement limited structural data, the inclusion of biochemical data is critical for achieving the accuracy and completeness necessary to analyze the specificity and competition between the protein interactions. Firstly, this procedure provides a means to clarify the information content of existing data on purported protein interactions and to remove indirect and spurious interactions. Secondly, the IIN we have constructed here for proteins involved in clathrin-mediated endocytosis (CME) exhibits distinctive topological properties. In contrast to PPI networks with their global and relatively dense connectivity, the fragmentation of the IIN into distinctive network modules suggests that different functional pressures act on the evolution of its topology. Large modules in the IIN are formed by interfaces sharing specificity for certain domain types, such as SH3 domains distributed across different proteins. The shared and distinct specificity of an interface is necessary for effective negative and positive design of highly selective binding targets. Lastly, the organization of detailed structural data in a network format allows one to identify pathways of specific binding interactions and thereby predict effects of mutations at specific surfaces on a protein and of specific binding inhibitors, as we explore in several examples. Overall, the endocytosis IIN is remarkably complex and rich in features masked in the coarser PPI, and collects relevant detail of protein association in a readily interpretable format.Margaret E JohnsonGerhard HummerPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 5, p e1003065 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Margaret E Johnson Gerhard Hummer Interface-resolved network of protein-protein interactions.
description	We define an interface-interaction network (IIN) to capture the specificity and competition between protein-protein interactions (PPI). This new type of network represents interactions between individual interfaces used in functional protein binding and thereby contains the detail necessary to describe the competition and cooperation between any pair of binding partners. Here we establish a general framework for the construction of IINs that merges computational structure-based interface assignment with careful curation of available literature. To complement limited structural data, the inclusion of biochemical data is critical for achieving the accuracy and completeness necessary to analyze the specificity and competition between the protein interactions. Firstly, this procedure provides a means to clarify the information content of existing data on purported protein interactions and to remove indirect and spurious interactions. Secondly, the IIN we have constructed here for proteins involved in clathrin-mediated endocytosis (CME) exhibits distinctive topological properties. In contrast to PPI networks with their global and relatively dense connectivity, the fragmentation of the IIN into distinctive network modules suggests that different functional pressures act on the evolution of its topology. Large modules in the IIN are formed by interfaces sharing specificity for certain domain types, such as SH3 domains distributed across different proteins. The shared and distinct specificity of an interface is necessary for effective negative and positive design of highly selective binding targets. Lastly, the organization of detailed structural data in a network format allows one to identify pathways of specific binding interactions and thereby predict effects of mutations at specific surfaces on a protein and of specific binding inhibitors, as we explore in several examples. Overall, the endocytosis IIN is remarkably complex and rich in features masked in the coarser PPI, and collects relevant detail of protein association in a readily interpretable format.
format	article
author	Margaret E Johnson Gerhard Hummer
author_facet	Margaret E Johnson Gerhard Hummer
author_sort	Margaret E Johnson
title	Interface-resolved network of protein-protein interactions.
title_short	Interface-resolved network of protein-protein interactions.
title_full	Interface-resolved network of protein-protein interactions.
title_fullStr	Interface-resolved network of protein-protein interactions.
title_full_unstemmed	Interface-resolved network of protein-protein interactions.
title_sort	interface-resolved network of protein-protein interactions.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/731b2839896f4570974294bc57cc90e3
work_keys_str_mv	AT margaretejohnson interfaceresolvednetworkofproteinproteininteractions AT gerhardhummer interfaceresolvednetworkofproteinproteininteractions
_version_	1718424735551848448

Interface-resolved network of protein-protein interactions.

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