2MKI

Solution structure of tandem RRM domains of cytoplasmic polyadenylation element binding protein 4 (CPEB4) in complex with RNA

Summary for 2MKI

• Entry DOI: 10.2210/pdb2mki/pdb
• Related: 2MKE 2MKH 2MKJ 2MKK
• NMR Information: BMRB: 19776
• Descriptor: Cytoplasmic polyadenylation element-binding protein 4, RNA (5'-R(*CP*UP*UP*UP*A)-3') (2 entities in total)
• Functional Keywords: cpeb4, cytoplasmic polyadenylation, rna recognition motif (rrm), protein-rna interaction, translational regulation, translation regulator-rna complex, translation regulator/rna
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 24333.91

Authors

Afroz, T.,Skrisovska, L.,Belloc, E.,Boixet, J.G.,Mendez, R.,Allain, F.H.-T. (deposition date: 2014-02-07, release date: 2014-07-23, Last modification date: 2024-05-01)

Primary citation

Afroz, T.,Skrisovska, L.,Belloc, E.,Guillen-Boixet, J.,Mendez, R.,Allain, F.H.-T.
A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins
Genes Dev., 28:1498-1514, 2014

PubMed Abstract: Cytoplasmic changes in polyA tail length is a key mechanism of translational control and is implicated in germline development, synaptic plasticity, cellular proliferation, senescence, and cancer progression. The presence of a U-rich cytoplasmic polyadenylation element (CPE) in the 3' untranslated regions (UTRs) of the responding mRNAs gives them the selectivity to be regulated by the CPE-binding (CPEB) family of proteins, which recognizes RNA via the tandem RNA recognition motifs (RRMs). Here we report the solution structures of the tandem RRMs of two human paralogs (CPEB1 and CPEB4) in their free and RNA-bound states. The structures reveal an unprecedented arrangement of RRMs in the free state that undergo an original closure motion upon RNA binding that ensures high fidelity. Structural and functional characterization of the ZZ domain (zinc-binding domain) of CPEB1 suggests a role in both protein-protein and protein-RNA interactions. Together with functional studies, the structures reveal how RNA binding by CPEB proteins leads to an optimal positioning of the N-terminal and ZZ domains at the 3' UTR, which favors the nucleation of the functional ribonucleoprotein complexes for translation regulation.

PubMed: 24990967
DOI: 10.1101/gad.241133.114

Experimental method

SOLUTION NMR