title: Structural insights into the transcriptional and translational roles of Ebp1.
abstract: The ErbB3-binding protein 1 (Ebp1) is an important regulator of transcription, affecting eukaryotic cell growth, proliferation, differentiation and survival. Ebp1 can also affect translation and cooperates with the polypyrimidine tract-binding protein (PTB) to stimulate the activity of the internal ribosome entry site (IRES) of foot-and-mouth disease virus (FMDV). We report here the crystal structure of murine Ebp1 (p48 isoform), providing the first glimpse of the architecture of this versatile regulator. The structure reveals a core domain that is homologous to methionine aminopeptidases, coupled to a C-terminal extension that contains important motifs for binding proteins and RNA. It sheds new light on the conformational differences between the p42 and p48 isoforms of Ebp1, the disposition of the key protein-interacting motif ((354)LKALL(358)) and the RNA-binding activity of Ebp1. We show that the primary RNA-binding site is formed by a Lys-rich motif in the C terminus and mediates the interaction with the FMDV IRES. We also demonstrate a specific functional requirement for Ebp1 in FMDV IRES-directed translation that is independent of a direct interaction with PTB.
authors: Division of Cell and Molecular Biology, Imperial College, South Kensington Campus, London, UK.
authors: Tom P
authors: TP
authors: Monie
authors: Andrew J
authors: AJ
authors: Perrin
authors: James R
authors: JR
authors: Birtley
authors: Trevor R
authors: TR
authors: Sweeney
authors: Ioannis
authors: I
authors: Karakasiliotis
authors: Yasmin
authors: Y
authors: Chaudhry
authors: Lisa O
authors: LO
authors: Roberts
authors: Stephen
authors: S
authors: Matthews
authors: Ian G
authors: IG
authors: Goodfellow
authors: Stephen
authors: S
authors: Curry
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000502:physiology; D000626:Aminopeptidases / Q000737:chemistry; D001665:Binding Sites; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics; D008239:Lysine / Q000737:chemistry; D063208:Methionyl Aminopeptidases; D008958:Models, Molecular; D014176:Protein Biosynthesis; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D012367:RNA, Viral / Q000737:chemistry; D015533:Transcriptional Activation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D012367:RNA, Viral; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases; D008239:Lysine
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