title: The bent conformation of poly(A)-binding protein induced by RNA-binding is required for its translational activation function.
abstract: A recent study revealed that poly(A)-binding protein (PABP) bound to poly(A) RNA exhibits a sharply bent configuration at the linker region between RNA-recognition motif 2 (RRM2) and RRM3, whereas free PABP exhibits a highly flexible linear configuration. However, the physiological role of the bent structure of mRNA-bound PABP remains unknown. We investigated a role of the bent structure of PABP by constructing a PABP variant that fails to form the poly(A)-dependent bent structure but maintains its poly(A)-binding activity. We found that the bent structure of PABP/poly(A) complex is required for PABP's efficient interaction with eIF4G and eIF4G/eIF4E complex. Moreover, the mutant PABP had compromised translation activation function and failed to augment the formation of 80S translation initiation complex in an in vitro translation system. These results suggest that the bent conformation of PABP, which is induced by the interaction with 3' poly(A) tail, mediates poly(A)-dependent translation by facilitating the interaction with eIF4G and the eIF4G/eIF4E complex. The preferential binding of the eIF4G/eIF4E complex to the bent PABP/poly(A) complex seems to be a mechanism discriminating the mRNA-bound PABPs participating in translation from the idling mRNA-unbound PABPs.
authors.affiliation: a Department of Life Sciences , Pohang University of Science and Technology (POSTECH) , Pohang, Gyeongbuk , South Korea.
authors.forename: Ka Young
authors.initials: KY
authors.lastname: Hong
authors.affiliation: b School of Interdisciplinary Bioscience & Bioengineering, Pohang University of Science and Technology (POSTECH) , Pohang, Gyeongbuk , South Korea.
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: a Department of Life Sciences , Pohang University of Science and Technology (POSTECH) , Pohang, Gyeongbuk , South Korea.
authors.forename: Sohyun
authors.initials: S
authors.lastname: Gu
authors.affiliation: a Department of Life Sciences , Pohang University of Science and Technology (POSTECH) , Pohang, Gyeongbuk , South Korea.
authors.forename: Eunah
authors.initials: E
authors.lastname: Kim
authors.affiliation: a Department of Life Sciences , Pohang University of Science and Technology (POSTECH) , Pohang, Gyeongbuk , South Korea.
authors.forename: Sihyeon
authors.initials: S
authors.lastname: An
authors.affiliation: a Department of Life Sciences , Pohang University of Science and Technology (POSTECH) , Pohang, Gyeongbuk , South Korea.
authors.forename: Junyoung
authors.initials: J
authors.lastname: Kwon
authors.affiliation: b School of Interdisciplinary Bioscience & Bioengineering, Pohang University of Science and Technology (POSTECH) , Pohang, Gyeongbuk , South Korea.|c Department of Physics , Pohang University of Science and Technology (POSTECH) , Pohang, Gyeongbuk , South Korea.
authors.forename: Jong-Bong
authors.initials: JB
authors.lastname: Lee
authors.affiliation: a Department of Life Sciences , Pohang University of Science and Technology (POSTECH) , Pohang, Gyeongbuk , South Korea.|b School of Interdisciplinary Bioscience & Bioengineering, Pohang University of Science and Technology (POSTECH) , Pohang, Gyeongbuk , South Korea.
authors.forename: Sung Key
authors.initials: SK
authors.lastname: Jang
mesh_terms: D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D039102:Poly(A)-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D039603:Eukaryotic Initiation Factor-4G; D046912:Multiprotein Complexes; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger
keywords: Bent structure; PABP; PABP-eIF4G interaction; poly(A) tail; translation