Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered

Abstract

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.

Autoren

Mariane Gonçalves-Kulik
Pablo Mier
Kristina Kastano
Juan Cortés
Pau Bernadó
Friederike Schmid
Miguel A Andrade-Navarro

DOI

10.3390/biom12081098

eISSN

2218-273X

Ausgabe der Veröffentlichung

8

Zeitschrift

Biomolecules

Sprache

en

Online publication date

2022

Paginierung

1098 - 1098

Status

Published online

Herausgeber

MDPI AG

Herausgeber URL

http://dx.doi.org/10.3390/biom12081098

Datum der Datenerfassung

2022

Titel

Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered

Ausgabe der Zeitschrift

12

Datenquelle: Crossref

Abstract

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.

Addresses

Institute of Organismic and Molecular Evolution, Faculty of Biology, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.

Autoren

Mariane Gonçalves-Kulik
Pablo Mier
Kristina Kastano
Juan Cortés
Pau Bernadó
Friederike Schmid
Miguel A Andrade-Navarro

DOI

10.3390/biom12081098

eISSN

2218-273X

Externe Identifier

PubMed Identifier: 36008992
PubMed Central ID: PMC9405754

Funding acknowledgements

European Council: 648030
European Research Council: 648030
European Council: N/D
French National Research Agency: ANR-19-P3IA-0004
European Council: ANR-10-LABX-12-01

Open access

true

ISSN

2218-273X

Ausgabe der Veröffentlichung

8

Zeitschrift

Biomolecules

Schlüsselwörter

Humans
Amino Acids
Proteins
Computational Biology
Protein Conformation
Databases, Protein
Intrinsically Disordered Proteins
Protein Domains

Sprache

eng

Medium

Electronic

Online publication date

2022

Open access status

Open Access

Paginierung

1098

Datum der Veröffentlichung

2022

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2022

Titel

Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered.

Sub types

Research Support, Non-U.S. Gov't
research-article
Journal Article

Ausgabe der Zeitschrift

12

Files

https://www.mdpi.com/2218-273X/12/8/1098/pdf?version=1660123535 https://europepmc.org/articles/PMC9405754?pdf=render

Datenquelle: Europe PubMed Central

Abstract

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.

Date of acceptance

2022

Autoren

Mariane Gonçalves-Kulik
Pablo Mier
Kristina Kastano
Juan Cortés
Pau Bernadó
Friederike Schmid
Miguel A Andrade-Navarro

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/36008992

DOI

10.3390/biom12081098

eISSN

2218-273X

Externe Identifier

PubMed Central ID: PMC9405754

Ausgabe der Veröffentlichung

8

Zeitschrift

Biomolecules

Schlüsselwörter

homorepeats
intrinsically disordered regions
low complexity regions
protein structure
Amino Acids
Computational Biology
Databases, Protein
Humans
Intrinsically Disordered Proteins
Protein Conformation
Protein Domains
Proteins

Sprache

eng

Country

Switzerland

PII

biom12081098

Datum der Veröffentlichung

2022

Status

Published online

Datum, an dem der Datensatz öffentlich gemacht wurde

2022

Titel

Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

12

Datenquelle: PubMed

Author's licence

CC-BY

Autoren

Mariane Gonçalves-Kulik
Pablo Mier
Kristina Kastano
Juan Cortés
Pau Bernadó
Friederike Schmid
Miguel A Andrade-Navarro

Hosting institution

Universitätsbibliothek Mainz

Sammlungen

DFG-491381577-G

Resource version

Published version

DOI

10.3390/biom12081098

File(s) embargoed

false

Open access

true

ISSN

2218-273X

Ausgabe der Veröffentlichung

8

Zeitschrift

Biomolecules

Schlüsselwörter

570 Biowissenschaften
570 Life sciences

Sprache

eng

Open access status

Open Access

Paginierung

1098

Datum der Veröffentlichung

2022

Public URL

https://openscience.ub.uni-mainz.de/handle/20.500.12030/10259

Herausgeber

MDPI

Datum der Datenerfassung

2024

Datum, an dem der Datensatz öffentlich gemacht wurde

2024

Zugang

Public

Titel

Low complexity induces structure in protein regions predicted as intrinsically disordered

Ausgabe der Zeitschrift

12

Files

low_complexity_induces_struct-20240318181104124.pdf

Datenquelle: OPENSCIENCE.UB

Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered

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