Differential interaction of PRMT1 with RGG-boxes of the FET family proteins EWS and TAF15.

The FET sub-family (FUS/TLS, EWS, TAF15) of RNA-binding proteins have remarkably similar overall structure but diverse biological and pathological roles. The molecular basis for FET protein specialisation is largely unknown. Gly-Arg-Rich regions (RGG-boxes) within FET proteins are targets for methylation by Protein-Arginine-Methyl-Transferase-1 (PRMT1) and substrate capture is thought to involve electrostatic attraction between positively charged polyRGG substrates and negatively charged surface channels of PRMT1. Unlike FUS and EWS, a high proportion of TAF15 RGG-boxes are embedded within neutrally charged YGGDR(S/G)G repeats, suggesting that they might not bind well to PRMT1. This notion runs contrary however to a report that YGGDR(S/G)G repeats are methylated by PRMT1. Using peptide-based polyRGG substrates and a novel 2-hybrid binding assay, we find that the Asp residue in YGGDR(S/G)G repeats confers poor binding to PRMT1. Our results therefore indicate that YGGDR(S/G)G repeats may contribute to TAF15 specialisation by enabling differential interactions with PRMT1 and reduced overall levels of TAF15 methylation compared with other FET proteins. By analogy with molecular recognition of other disordered polyvalent ligands by globular protein partners, we also propose a dynamic polyelectrostatic model for substrate capture by PRMT1. This article is protected by copyright. All rights reserved. © 2017 The Protein Society.

Citation

Kim K C Li, Bess L Chau, Kevin A W Lee. Differential interaction of PRMT1 with RGG-boxes of the FET family proteins EWS and TAF15. Protein science : a publication of the Protein Society. 2017 Nov 30

PMID: 29193371

search → result