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Interaction modulation through arrays of clustered methyl-arginine protein modifications

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Item Type:Article
Title:Interaction modulation through arrays of clustered methyl-arginine protein modifications
Creators Name:Woodsmith, J. and Casado-Medrano, V. and Benlasfer, N. and Eccles, R.L. and Hutten, S. and Heine, C.L. and Thormann, V. and Abou-Ajram, C. and Rocks, O. and Dormann, D. and Stelzl, U.
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.
Source:Life Science Alliance
Publisher:Life Science Alliance
Page Range:e201800178
Date:October 2018
Official Publication:https://doi.org/10.26508/lsa.201800178
PubMed:View item in PubMed

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