4f26
Crystal structure of the second RRM domain of human PABPC1 a pH 9.0Crystal structure of the second RRM domain of human PABPC1 a pH 9.0
Structural highlights
FunctionPABP1_HUMAN Binds the poly(A) tail of mRNA. May be involved in cytoplasmic regulatory processes of mRNA metabolism such as pre-mRNA splicing. Its function in translational initiation regulation can either be enhanced by PAIP1 or repressed by PAIP2. Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo. Involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Involved in regulation of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons; for the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed.[1] [2] Publication Abstract from PubMedMany RNA-binding proteins contain multiple single-strand nucleic acid-binding domains and assemble into large multiprotein messenger ribonucleic acid protein (mRNP) complexes. The mechanisms underlying the self-assembly of these complexes are largely unknown. In eukaryotes, the association of the translation factors polyadenylate-binding protein-1 (PABP) and eIF4G is essential for high-level expression of polyadenylated mRNAs. Here, we report the crystal structure of the ternary complex poly(A)(11).PABP(1-190).eIF4G(178-203) at 2.0 A resolution. Our NMR and crystallographic data show that eIF4G interacts with the RRM2 domain of PABP. Analysis of the interaction by small-angle X-ray scattering, isothermal titration calorimetry, and electromobility shift assays reveals that this interaction is allosterically regulated by poly(A) binding to PABP. Furthermore, we have confirmed the importance of poly(A) for the endogenous PABP and eIF4G interaction in immunoprecipitation experiments using HeLa cell extracts. Our findings reveal interdomain allostery as a mechanism for cooperative assembly of RNP complexes. Interdomain Allostery Promotes Assembly of the Poly(A) mRNA Complex with PABP and eIF4G.,Safaee N, Kozlov G, Noronha AM, Xie J, Wilds CJ, Gehring K Mol Cell. 2012 Nov 9;48(3):375-86. doi: 10.1016/j.molcel.2012.09.001. Epub 2012, Oct 4. PMID:23041282[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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