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The Role of Low Complexity Regions in Protein Interaction Modes: An Illustration in Huntingtin

Low complexity regions (LCRs) are very frequent in protein sequences, generally having a lower propensity to form structured domains and tending to be much less evolutionarily conserved than globular domains. Their higher abundance in eukaryotes and in species with more cellular types agrees with a...

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Autores principales: Kastano, Kristina, Mier, Pablo, Andrade-Navarro, Miguel A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915032/
https://www.ncbi.nlm.nih.gov/pubmed/33572172
http://dx.doi.org/10.3390/ijms22041727
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author Kastano, Kristina
Mier, Pablo
Andrade-Navarro, Miguel A.
author_facet Kastano, Kristina
Mier, Pablo
Andrade-Navarro, Miguel A.
author_sort Kastano, Kristina
collection PubMed
description Low complexity regions (LCRs) are very frequent in protein sequences, generally having a lower propensity to form structured domains and tending to be much less evolutionarily conserved than globular domains. Their higher abundance in eukaryotes and in species with more cellular types agrees with a growing number of reports on their function in protein interactions regulated by post-translational modifications. LCRs facilitate the increase of regulatory and network complexity required with the emergence of organisms with more complex tissue distribution and development. Although the low conservation and structural flexibility of LCRs complicate their study, evolutionary studies of proteins across species have been used to evaluate their significance and function. To investigate how to apply this evolutionary approach to the study of LCR function in protein–protein interactions, we performed a detailed analysis for Huntingtin (HTT), a large protein that is a hub for interaction with hundreds of proteins, has a variety of LCRs, and for which partial structural information (in complex with HAP40) is available. We hypothesize that proteins RASA1, SYN2, and KAT2B may compete with HAP40 for their attachment to the core of HTT using similar LCRs. Our results illustrate how evolution might favor the interplay of LCRs with domains, and the possibility of detecting multiple modes of LCR-mediated protein–protein interactions with a large hub such as HTT when enough protein interaction data is available.
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spelling pubmed-79150322021-03-01 The Role of Low Complexity Regions in Protein Interaction Modes: An Illustration in Huntingtin Kastano, Kristina Mier, Pablo Andrade-Navarro, Miguel A. Int J Mol Sci Article Low complexity regions (LCRs) are very frequent in protein sequences, generally having a lower propensity to form structured domains and tending to be much less evolutionarily conserved than globular domains. Their higher abundance in eukaryotes and in species with more cellular types agrees with a growing number of reports on their function in protein interactions regulated by post-translational modifications. LCRs facilitate the increase of regulatory and network complexity required with the emergence of organisms with more complex tissue distribution and development. Although the low conservation and structural flexibility of LCRs complicate their study, evolutionary studies of proteins across species have been used to evaluate their significance and function. To investigate how to apply this evolutionary approach to the study of LCR function in protein–protein interactions, we performed a detailed analysis for Huntingtin (HTT), a large protein that is a hub for interaction with hundreds of proteins, has a variety of LCRs, and for which partial structural information (in complex with HAP40) is available. We hypothesize that proteins RASA1, SYN2, and KAT2B may compete with HAP40 for their attachment to the core of HTT using similar LCRs. Our results illustrate how evolution might favor the interplay of LCRs with domains, and the possibility of detecting multiple modes of LCR-mediated protein–protein interactions with a large hub such as HTT when enough protein interaction data is available. MDPI 2021-02-09 /pmc/articles/PMC7915032/ /pubmed/33572172 http://dx.doi.org/10.3390/ijms22041727 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kastano, Kristina
Mier, Pablo
Andrade-Navarro, Miguel A.
The Role of Low Complexity Regions in Protein Interaction Modes: An Illustration in Huntingtin
title The Role of Low Complexity Regions in Protein Interaction Modes: An Illustration in Huntingtin
title_full The Role of Low Complexity Regions in Protein Interaction Modes: An Illustration in Huntingtin
title_fullStr The Role of Low Complexity Regions in Protein Interaction Modes: An Illustration in Huntingtin
title_full_unstemmed The Role of Low Complexity Regions in Protein Interaction Modes: An Illustration in Huntingtin
title_short The Role of Low Complexity Regions in Protein Interaction Modes: An Illustration in Huntingtin
title_sort role of low complexity regions in protein interaction modes: an illustration in huntingtin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915032/
https://www.ncbi.nlm.nih.gov/pubmed/33572172
http://dx.doi.org/10.3390/ijms22041727
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