2m13 | pdb_00002m13
The ZZ domain of cytoplasmic polyadenylation element binding protein 1 (CPEB1)
Structural highlights
FunctionCPEB1_HUMAN Sequence-specific RNA-binding protein that regulates mRNA cytoplasmic polyadenylation and translation initiation during oocyte maturation, early development and at postsynapse sites of neurons. Binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5'-UUUUUAU-3') within the mRNA 3'-UTR. In absence of phosphorylation and in association with TACC3 is also involved as a repressor of translation of CPE-containing mRNA; a repression that is relieved by phosphorylation or degradation (By similarity). Involved in the transport of CPE-containing mRNA to dendrites; those mRNAs may be transported to dendrites in a translationally dormant form and translationally activated at synapses (By similarity). Its interaction with APLP1 promotes local CPE-containing mRNA polyadenylation and translation activation (By similarity). Induces the assembly of stress granules in the absence of stress.[1] [2] Publication Abstract from PubMedCytoplasmic polyadenylation element binding protein (CPEB) provides temporal and spatial control of protein synthesis required for early development and neuronal synaptic plasticity. CPEB regulates protein expression by inhibiting polyadenylation of selected mRNA transcripts, which prevents binding of the ribosome for protein synthesis. Two RNA recognition motif domains and a C-terminal binuclear zinc-binding domain are required for mRNA binding, but the zinc-binding domain is not required for sequence-specific recognition of the targeted mRNA transcript. The structure and function of the zinc-binding domain of CPEB are unknown. The C-terminal region of CPEB may participate in assembly of the ribonucleoprotein complex that includes the scaffold protein, Symplekin, and the cleavage and polyadenylation specificity factor. Sumoylation of Symplekin is required for polyadenylation, and both cleavage and polyadenylation specificity factor and poly(A) polymerase are sumoylated. The foreshortened poly(A) tail is maintained by poly(A) ribonuclease, which associates with CPEB. While zinc-binding domains are renowned for nucleic acid recognition, binuclear zinc-binding structural motifs, such as LIM (Lin-11, Isl-1, Mec-3), RING (really interesting new gene), PHD (plant homeodomain) and ZZ (ZZ-type zinc finger) domains, participate in protein-protein interactions. Here, we report the solution structure of the C-terminal zinc-binding domain of CPEB1 (CPEB1-ZZ), which has a cross-braced zinc binding topology. The structural similarity to other ZZ domains suggests that the CPEB1-ZZ domain recruits sumoylated proteins during assembly of the ribonucleoprotein complex prior to mRNA export from the nucleus. The C-Terminal Region of Cytoplasmic Polyadenylation Element Binding Protein Is a ZZ Domain with Potential for Protein-Protein Interactions.,Merkel DJ, Wells SB, Hilburn BC, Elazzouzi F, Perez-Alvarado GC, Lee BM J Mol Biol. 2013 Mar 13. pii: S0022-2836(13)00156-3. doi:, 10.1016/j.jmb.2013.03.009. PMID:23500490[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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