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Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered

There is increasing evidence that many intrinsically disordered regions (IDRs) in proteins play key functional roles through interactions with other proteins or nucleic acids. These interactions often exhibit a context-dependent structural behavior. We hypothesize that low complexity regions (LCRs),...

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Autores principales: Gonçalves-Kulik, Mariane, Mier, Pablo, Kastano, Kristina, Cortés, Juan, Bernadó, Pau, Schmid, Friederike, Andrade-Navarro, Miguel A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405754/
https://www.ncbi.nlm.nih.gov/pubmed/36008992
http://dx.doi.org/10.3390/biom12081098
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author Gonçalves-Kulik, Mariane
Mier, Pablo
Kastano, Kristina
Cortés, Juan
Bernadó, Pau
Schmid, Friederike
Andrade-Navarro, Miguel A.
author_facet Gonçalves-Kulik, Mariane
Mier, Pablo
Kastano, Kristina
Cortés, Juan
Bernadó, Pau
Schmid, Friederike
Andrade-Navarro, Miguel A.
author_sort Gonçalves-Kulik, Mariane
collection PubMed
description There is increasing evidence that many intrinsically disordered regions (IDRs) in proteins play key functional roles through interactions with other proteins or nucleic acids. These interactions often exhibit a context-dependent structural behavior. We hypothesize that low complexity regions (LCRs), often found within IDRs, could have a role in inducing local structure in IDRs. To test this, we predicted IDRs in the human proteome and analyzed their structures or those of homologous sequences in the Protein Data Bank (PDB). We then identified two types of simple LCRs within IDRs: regions with only one (polyX or homorepeats) or with only two types of amino acids (polyXY). We were able to assign structural information from the PDB more often to these LCRs than to the surrounding IDRs (polyX 61.8% > polyXY 50.5% > IDRs 39.7%). The most frequently observed polyX and polyXY within IDRs contained E (Glu) or G (Gly). Structural analyses of these sequences and of homologs indicate that polyEK regions induce helical conformations, while the other most frequent LCRs induce coil structures. Our work proposes bioinformatics methods to help in the study of the structural behavior of IDRs and provides a solid basis suggesting a structuring role of LCRs within them.
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spelling pubmed-94057542022-08-26 Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered Gonçalves-Kulik, Mariane Mier, Pablo Kastano, Kristina Cortés, Juan Bernadó, Pau Schmid, Friederike Andrade-Navarro, Miguel A. Biomolecules Article There is increasing evidence that many intrinsically disordered regions (IDRs) in proteins play key functional roles through interactions with other proteins or nucleic acids. These interactions often exhibit a context-dependent structural behavior. We hypothesize that low complexity regions (LCRs), often found within IDRs, could have a role in inducing local structure in IDRs. To test this, we predicted IDRs in the human proteome and analyzed their structures or those of homologous sequences in the Protein Data Bank (PDB). We then identified two types of simple LCRs within IDRs: regions with only one (polyX or homorepeats) or with only two types of amino acids (polyXY). We were able to assign structural information from the PDB more often to these LCRs than to the surrounding IDRs (polyX 61.8% > polyXY 50.5% > IDRs 39.7%). The most frequently observed polyX and polyXY within IDRs contained E (Glu) or G (Gly). Structural analyses of these sequences and of homologs indicate that polyEK regions induce helical conformations, while the other most frequent LCRs induce coil structures. Our work proposes bioinformatics methods to help in the study of the structural behavior of IDRs and provides a solid basis suggesting a structuring role of LCRs within them. MDPI 2022-08-10 /pmc/articles/PMC9405754/ /pubmed/36008992 http://dx.doi.org/10.3390/biom12081098 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gonçalves-Kulik, Mariane
Mier, Pablo
Kastano, Kristina
Cortés, Juan
Bernadó, Pau
Schmid, Friederike
Andrade-Navarro, Miguel A.
Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered
title Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered
title_full Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered
title_fullStr Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered
title_full_unstemmed Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered
title_short Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered
title_sort low complexity induces structure in protein regions predicted as intrinsically disordered
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405754/
https://www.ncbi.nlm.nih.gov/pubmed/36008992
http://dx.doi.org/10.3390/biom12081098
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