Interaction modulation through arrays of clustered methyl-arginine protein modifications

Publication type:

Journal article

Metadata:

Autoren

Jonathan Woodsmith
Victoria Casado-Medrano
Nouhad Benlasfer
Rebecca L Eccles
Saskia Hutten
Christian L Heine
Verena Thormann
Claudia Abou-Ajram
Oliver Rocks
Dorothee Dormann
Ulrich Stelzl

Autoren-URL

https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000457334100015&DestLinkType=FullRecord&DestApp=WOS_CPL

DOI

10.26508/lsa.201800178

eISSN

2575-1077

Externe Identifier

Clarivate Analytics Document Solution ID: HJ6WO
PubMed Identifier: 30456387

Ausgabe der Veröffentlichung

Zeitschrift

LIFE SCIENCE ALLIANCE

Artikelnummer

ARTN e201800178

Datum der Veröffentlichung

2018

Status

Published

Titel

Interaction modulation through arrays of clustered methyl-arginine protein modifications

Sub types

Article

Ausgabe der Zeitschrift

Data source: Web of Science (Lite)

Other metadata sources:

Abstract

Systematic analysis of human arginine methylation identifies two distinct signaling modes; either isolated modifications akin to canonical post-translational modification regulation, or clustered arrays within disordered protein sequence. Hundreds of proteins contain these methyl-arginine arrays and are more prone to accumulate mutations and more tightly expression-regulated than dispersed methylation targets. Arginines within an array in the highly methylated RNA-binding protein synaptotagmin binding cytoplasmic RNA interacting protein (SYNCRIP) were experimentally shown to function in concert, providing a tunable protein interaction interface. Quantitative immunoprecipitation assays defined two distinct cumulative binding mechanisms operating across 18 proximal arginine–glycine (RG) motifs in SYNCRIP. Functional binding to the methyltransferase PRMT1 was promoted by continual arginine stretches, whereas interaction with the methyl-binding protein SMN1 was arginine content–dependent irrespective of linear position within the unstructured region. This study highlights how highly repetitive modifiable amino acid arrays in low structural complexity regions can provide regulatory platforms, with SYNCRIP as an extreme example how arginine methylation leverages these disordered sequences to mediate cellular interactions.

Autoren

Jonathan Woodsmith
Victoria Casado-Medrano
Nouhad Benlasfer
Rebecca L Eccles
Saskia Hutten
Christian L Heine
Verena Thormann
Claudia Abou-Ajram
Oliver Rocks
Dorothee Dormann
Ulrich Stelzl

DOI

10.26508/lsa.201800178

eISSN

2575-1077

Ausgabe der Veröffentlichung

Zeitschrift

Life Science Alliance

Sprache

Online publication date

2018

Paginierung

e201800178 - e201800178

Datum der Veröffentlichung

2018

Status

Published

Herausgeber

Life Science Alliance, LLC

Herausgeber URL

http://dx.doi.org/10.26508/lsa.201800178

Datum der Datenerfassung

2024

Titel

Interaction modulation through arrays of clustered methyl-arginine protein modifications

Ausgabe der Zeitschrift

Data source: Crossref

Abstract

Systematic analysis of human arginine methylation identifies two distinct signaling modes; either isolated modifications akin to canonical post-translational modification regulation, or clustered arrays within disordered protein sequence. Hundreds of proteins contain these methyl-arginine arrays and are more prone to accumulate mutations and more tightly expression-regulated than dispersed methylation targets. Arginines within an array in the highly methylated RNA-binding protein synaptotagmin binding cytoplasmic RNA interacting protein (SYNCRIP) were experimentally shown to function in concert, providing a tunable protein interaction interface. Quantitative immunoprecipitation assays defined two distinct cumulative binding mechanisms operating across 18 proximal arginine-glycine (RG) motifs in SYNCRIP. Functional binding to the methyltransferase PRMT1 was promoted by continual arginine stretches, whereas interaction with the methyl-binding protein SMN1 was arginine content-dependent irrespective of linear position within the unstructured region. This study highlights how highly repetitive modifiable amino acid arrays in low structural complexity regions can provide regulatory platforms, with SYNCRIP as an extreme example how arginine methylation leverages these disordered sequences to mediate cellular interactions.

Addresses

Institute of Pharmaceutical Sciences and BioTechMed-Graz, University of Graz, Graz, Austria.

Autoren

Jonathan Woodsmith
Victoria Casado-Medrano
Nouhad Benlasfer
Rebecca L Eccles
Saskia Hutten
Christian L Heine
Verena Thormann
Claudia Abou-Ajram
Oliver Rocks
Dorothee Dormann
Ulrich Stelzl

DOI

10.26508/lsa.201800178

eISSN

2575-1077

Externe Identifier

PubMed Identifier: 30456387
PubMed Central ID: PMC6238616

Funding acknowledgements

Munich Cluster for Systems Neurology: EXC 1010
Deutsche Forschungsgemeinschaft (German Research Foundation): DO 1804/1-1
Ludwig-Maximilians-Universität München:
Max-Planck Society:
University of Graz:

Open access

true

ISSN

2575-1077

Ausgabe der Veröffentlichung

Zeitschrift

Life science alliance

Sprache

eng

Medium

Electronic-eCollection

Online publication date

2018

Open access status

Open Access

Paginierung

e201800178

Datum der Veröffentlichung

2018

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2018

Titel

Interaction modulation through arrays of clustered methyl-arginine protein modifications.

Sub types

research-article
Journal Article

Ausgabe der Zeitschrift

Files

https://www.life-science-alliance.org/content/lsa/1/5/e201800178.full.pdf https://europepmc.org/articles/PMC6238616?pdf=render

Data source: Europe PubMed Central

Abstract

Systematic analysis of human arginine methylation identifies two distinct signaling modes; either isolated modifications akin to canonical post-translational modification regulation, or clustered arrays within disordered protein sequence. Hundreds of proteins contain these methyl-arginine arrays and are more prone to accumulate mutations and more tightly expression-regulated than dispersed methylation targets. Arginines within an array in the highly methylated RNA-binding protein synaptotagmin binding cytoplasmic RNA interacting protein (SYNCRIP) were experimentally shown to function in concert, providing a tunable protein interaction interface. Quantitative immunoprecipitation assays defined two distinct cumulative binding mechanisms operating across 18 proximal arginine-glycine (RG) motifs in SYNCRIP. Functional binding to the methyltransferase PRMT1 was promoted by continual arginine stretches, whereas interaction with the methyl-binding protein SMN1 was arginine content-dependent irrespective of linear position within the unstructured region. This study highlights how highly repetitive modifiable amino acid arrays in low structural complexity regions can provide regulatory platforms, with SYNCRIP as an extreme example how arginine methylation leverages these disordered sequences to mediate cellular interactions.

Date of acceptance

2018

Autoren

Jonathan Woodsmith
Victoria Casado-Medrano
Nouhad Benlasfer
Rebecca L Eccles
Saskia Hutten
Christian L Heine
Verena Thormann
Claudia Abou-Ajram
Oliver Rocks
Dorothee Dormann
Ulrich Stelzl

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/30456387

DOI

10.26508/lsa.201800178

eISSN

2575-1077

Externe Identifier

PubMed Central ID: PMC6238616

Ausgabe der Veröffentlichung

Zeitschrift

Life Sci Alliance

Sprache

eng

Country

United States

Paginierung

e201800178

PII

LSA-2018-00178

Datum der Veröffentlichung

2018

Status

Published online

Titel

Interaction modulation through arrays of clustered methyl-arginine protein modifications.

Sub types

Journal Article

Ausgabe der Zeitschrift

Data source: PubMed

Beziehungen:

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