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SOLUTION STRUCTURE OF C-TERMINAL DOMAIN OF POLY(A) BINDING PROTEIN FROM SACCHAROMYCES CEREVISIAESOLUTION STRUCTURE OF C-TERMINAL DOMAIN OF POLY(A) BINDING PROTEIN FROM SACCHAROMYCES CEREVISIAE
Structural highlights
FunctionPABP_YEAST Binds the poly(A) tail of mRNA. Appears to be an important mediator of the multiple roles of the poly(A) tail in mRNA biogenesis, stability and translation. In the nucleus, interacts with the nuclear cleavage factor IA (CFIA), which is required for both mRNA cleavage and polyadenylation. Is also required for efficient mRNA export to the cytoplasm. Acts in concert with a poly(A)-specific nuclease (PAN) to affect poly(A) tail shortening, which may occur concomitantly with either nucleocytoplasmic mRNA transport or translational initiation. Regulates PAN activity via interaction with the stimulator PAN3 or the inhibitor PBP1. In the cytoplasm, affects both translation and mRNA decay. Stimulates translation by interaction with translation initiation factor eIF4G, a subunit of the cap-binding complex eIF4F, bringing the 5'- and 3'-ends of the mRNA in proximity. The formation of this circular mRNP structure appears to be critical for the synergistic effects of the cap and the poly(A) tail in facilitating translation initiation, recycling of ribosomes, and mRNA stability. Also regulates translation termination by recruiting eukaryotic release factor 3 (eRF3). Interaction with eRF3 is also required for regulation of normal mRNA decay through translation termination-coupled poly(A) shortening, probably mediated by PAN. Loss of PAB1 from the mRNP after deadenylation triggers mRNA degradation. Inhibits the major cytoplasmic mRNA deadenylase CCR4-NOT complex. Is also associated peripherally with COPI vesicles through its interaction with ARF1, and this is required for correct localization of the asymmetrically distributed ASH1 mRNA.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe have determined the solution structure of the PABC domain from Saccharomyces cerevisiae Pab1p and mapped its peptide-binding site. PABC domains are peptide binding domains found in poly(A)-binding proteins (PABP) and are a subset of HECT-family E3 ubiquitin ligases (also known as hyperplastic discs proteins (HYDs)). In mammals, the PABC domain of PABP functions to recruit several different translation factors to the mRNA poly(A) tail. PABC domains are highly conserved, with high specificity for peptide sequences of roughly 12 residues with conserved alanine, phenylalanine, and proline residues at positions 7, 10, and 12. Compared with human PABP, the yeast PABC domain is missing the first alpha helix, contains two extra amino acids between helices 2 and 3, and has a strongly bent C-terminal helix. These give rise to unique peptide binding specificity wherein yeast PABC binds peptides from Paip2 and RF3 but not Paip1. Mapping of the peptide-binding site reveals that the bend in the C-terminal helix disrupts binding interactions with the N terminus of peptide ligands and leads to greatly reduced binding affinity for the peptides tested. No high affinity or natural binding partners from S. cerevisiae could be identified by sequence analysis of known PABC ligands. Comparison of the three known PABC structures shows that the features responsible for peptide binding are highly conserved and responsible for the distinct but overlapping binding specificities. Solution structure of the orphan PABC domain from Saccharomyces cerevisiae poly(A)-binding protein.,Kozlov G, Siddiqui N, Coillet-Matillon S, Trempe JF, Ekiel I, Sprules T, Gehring K J Biol Chem. 2002 Jun 21;277(25):22822-8. Epub 2002 Apr 8. PMID:11940585[15] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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