title: Crystal structure of the middle domain of human poly(A)-binding protein-interacting protein 1.
abstract: 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 α-helices and two antiparallel β-strands forming a β-hairpin. The 10 α-helices are arranged as five HEAT repeats which form a double layer of α 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.
authors.affiliation: Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, Ratzeburger Allee 160, Lübeck, Germany.
authors.forename: Jian
authors.initials: J
authors.lastname: Lei
authors.forename: Jeroen R
authors.initials: JR
authors.lastname: Mesters
authors.forename: Albrecht
authors.initials: A
authors.lastname: von Brunn
authors.forename: Rolf
authors.initials: R
authors.lastname: Hilgenfeld
mesh_terms: D000595:Amino Acid Sequence; D003461:Crystallography; D039603:Eukaryotic Initiation Factor-4G / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000737:chemistry* / Q000235:genetics; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry
chemical_list: D039603:Eukaryotic Initiation Factor-4G; C111580:PAIP1 protein, human; D010448:Peptide Initiation Factors; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C107740:TIF4631 protein, S cerevisiae