1jh4
From Proteopedia
Solution structure of the C-terminal PABC domain of human poly(A)-binding protein in complex with the peptide from Paip1
Structural highlights
Function[PABP1_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] [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.[3] [4] 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 PubMedThe C-terminal domain of poly(A)-binding protein (PABC) is a peptide-binding domain found in poly(A)-binding proteins (PABPs) and a HECT (homologous to E6-AP C-terminus) family E3 ubiquitin ligase. In protein synthesis, the PABC domain of PABP functions to recruit several translation factors possessing the PABP-interacting motif 2 (PAM2) to the mRNA poly(A) tail. We have determined the solution structure of the human PABC domain in complex with two peptides from PABP-interacting protein-1 (Paip1) and Paip2. The structures show a novel mode of peptide recognition, in which the peptide binds as a pair of beta-turns with extensive hydrophobic, electrostatic and aromatic stacking interactions. Mutagenesis of PABC and peptide residues was used to identify key protein-peptide interactions and quantified by isothermal calorimetry, surface plasmon resonance and GST pull-down assays. The results provide insight into the specificity of PABC in mediating PABP-protein interactions. Structural basis of ligand recognition by PABC, a highly specific peptide-binding domain found in poly(A)-binding protein and a HECT ubiquitin ligase.,Kozlov G, De Crescenzo G, Lim NS, Siddiqui N, Fantus D, Kahvejian A, Trempe JF, Elias D, Ekiel I, Sonenberg N, O'Connor-McCourt M, Gehring K EMBO J. 2004 Jan 28;23(2):272-81. Epub 2003 Dec 18. PMID:14685257[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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