DSSR-PyMOL cartoon-block schematics: PDB entry 5wwf

PDB-id

5wwf; DSSR-derived features in text and JSON formats

Class

RNA binding protein-RNA

Method

X-ray (2.15 Å)

Summary

Crystal structure of hnrnpa2b1 in complex with RNA

Reference

Wu B, Su S, Patil DP, Liu H, Gan J, Jaffrey SR, Ma J (2018): "Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1." Nat Commun, 9, 420. doi: 10.1038/s41467-017-02770-z.

Abstract

Human hnRNP A2/B1 is an RNA-binding protein that plays important roles in many biological processes, including maturation, transport, and metabolism of mRNA, and gene regulation of long noncoding RNAs. hnRNP A2/B1 was reported to control the microRNAs sorting to exosomes and promote primary microRNA processing as a potential m₆A "reader." hnRNP A2/B1 contains two RNA recognition motifs that provide sequence-specific recognition of RNA substrates. Here, we determine crystal structures of tandem RRM domains of hnRNP A2/B1 in complex with various RNA substrates, elucidating specific recognitions of AGG and UAG motifs by RRM1 and RRM2 domains, respectively. Further structural and biochemical results demonstrate multivariant binding modes for sequence-diversified RNA substrates, supporting a RNA matchmaker mechanism in hnRNP A2/B1 function. Moreover, our studies in combination with bioinformatic analysis suggest that hnRNP A2/B1 may mediate effects of m₆A through a "m₆A switch" mechanism, instead of acting as a direct "reader" of m₆A modification.