Summary information and primary citation
- PDB-id
-
6g2k;
DSSR-derived features in text and
JSON formats
- Class
- RNA binding protein
- Method
- X-ray (2.01 Å)
- Summary
- Structure of hur rrm3 in complex with RNA (uuuuuu)
- Reference
-
Pabis M, Popowicz GM, Stehle R, Fernandez-Ramos D, Asami
S, Warner L, Garcia-Maurino SM, Schlundt A,
Martinez-Chantar ML, Diaz-Moreno I, Sattler M (2019):
"HuR
biological function involves RRM3-mediated dimerization
and RNA binding by all three RRMs." Nucleic Acids
Res., 47, 1011-1029. doi: 10.1093/nar/gky1138.
- Abstract
- HuR/ELAVL1 is an RNA-binding protein involved in
differentiation and stress response that acts primarily by
stabilizing messenger RNA (mRNA) targets. HuR comprises
three RNA recognition motifs (RRMs) where the structure and
RNA binding of RRM3 and of full-length HuR remain poorly
understood. Here, we report crystal structures of RRM3 free
and bound to cognate RNAs. Our structural, NMR and
biochemical data show that RRM3 mediates canonical RNA
interactions and reveal molecular details of a dimerization
interface localized on the α-helical face of RRM3. NMR and
SAXS analyses indicate that the three RRMs in full-length
HuR are flexibly connected in the absence of RNA, while
they adopt a more compact arrangement when bound to RNA.
Based on these data and crystal structures of tandem
RRM1,2-RNA and our RRM3-RNA complexes, we present a
structural model of RNA recognition involving all three RRM
domains of full-length HuR. Mutational analysis
demonstrates that RRM3 dimerization and RNA binding is
required for functional activity of full-length HuR in
vitro and to regulate target mRNAs levels in human cells,
thus providing a fine-tuning for HuR activity in vivo.
