Interaction modulation through arrays of clustered methyl-arginine protein modifications
| Autor: | Claudia Abou-Ajram, Rebecca L Eccles, Verena Thormann, Oliver Rocks, Dorothee Dormann, Victoria Casado-Medrano, Nouhad Benlasfer, Saskia Hutten, Ulrich Stelzl, Christian L. Heine, Jonathan Woodsmith |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Methyltransferase Arginine Immunoprecipitation Health Toxicology and Mutagenesis Cellular functions RNA-binding protein Computational biology Plant Science medicine.disease_cause Biochemistry Genetics and Molecular Biology (miscellaneous) Synaptotagmin 1 03 medical and health sciences 0302 clinical medicine Protein sequencing medicine Research Articles chemistry.chemical_classification Mutation Ecology Chemistry RNA Methylation Cell biology Amino acid 030104 developmental biology Interaction interface Function (biology) 030217 neurology & neurosurgery Research Article |
| Zdroj: | Life Science Alliance |
| DOI: | 10.1101/289041 |
| Popis: | Extensively modifiable arrays of clustered arginines in a large set of human proteins function as regulatory protein interaction platforms. Quantitative immunoprecipitation assays defined two distinct cumulative binding mechanisms operating across an array of 18 methyl-arginine motifs in SYNCRIP. 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. |
| Databáze: | OpenAIRE |
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