Structural highlights
Function
[PAIP1_HUMAN] Acts as a coactivator in the regulation of translation initiation of poly(A)-containing mRNAs. Its stimulatory activity on translation is mediated via its action on PABPC1. Competes with PAIP2 for binding to PABPC1. Its association with EIF4A and PABPC1 may potentiate contacts between mRNA termini. May also be 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.[1] [2]
Publication Abstract from PubMed
In eukaryotes, the poly(A)-binding protein (PABP) is one of the important factors for initiation of messenger RNA translation. PABP activity is regulated by the PABP-interacting proteins (Paips), which include Paip1, Paip2A, and Paip2B. Human Paip1 has three different isoforms. Here, we report the crystal structure of the middle domain of Paip1 isoform 2 (Paip1M) as determined by single-wavelength anomalous dispersion phasing. The structure reveals a crescent-shaped domain consisting of 10 alpha-helices and two antiparallel beta-strands forming a beta-hairpin. The 10 alpha-helices are arranged as five HEAT repeats which form a double layer of alpha helices with a convex and a concave surface. Despite low sequence identity, the overall fold of Paip1M is similar to the middle domain of human eIF4GII and yeast eIF4GI. Moreover, the amino-acid sequence motif and the local structure of eIF4G involved in binding of eIF4A, are conserved in Paip1. The structure reported here is the first of a member of the Paip family, thereby filling a gap in our understanding of initiation of eukaryotic mRNA translation in three dimensions.
Crystal structure of the middle domain of human poly(A)-binding protein-interacting protein 1.,Lei J, Mesters JR, Brunn AV, Hilgenfeld R Biochem Biophys Res Commun. 2011 Apr 23. PMID:21539810[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Craig AW, Haghighat A, Yu AT, Sonenberg N. Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation. Nature. 1998 Apr 2;392(6675):520-3. PMID:9548260 doi:10.1038/33198
- ↑ Grosset C, Chen CY, Xu N, Sonenberg N, Jacquemin-Sablon H, Shyu AB. A mechanism for translationally coupled mRNA turnover: interaction between the poly(A) tail and a c-fos RNA coding determinant via a protein complex. Cell. 2000 Sep 29;103(1):29-40. PMID:11051545
- ↑ Lei J, Mesters JR, Brunn AV, Hilgenfeld R. Crystal structure of the middle domain of human poly(A)-binding protein-interacting protein 1. Biochem Biophys Res Commun. 2011 Apr 23. PMID:21539810 doi:10.1016/j.bbrc.2011.04.088
