6H7B

Structure of Leishmania PABP1 (domain J) complexed with a peptide containing the PAM2 motif of eIF4E4.

6H7B の概要

• エントリーDOI: 10.2210/pdb6h7b/pdb
• 分子名称: Polyadenylate-binding protein, HIS-HIS-MET-ASN-PRO-ASN-ALA-THR-GLU-PHE-MET-PRO (3 entities in total)
• 機能のキーワード: complex translation initiation leishmania, translation
• 由来する生物種: Leishmania major; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 24898.56

構造登録者

Cameron, A.D.,Firczuk, H.,dos Santos Rodrigues, F.H.,McCarthy, J.E.G. (登録日: 2018-07-31, 公開日: 2018-12-12, 最終更新日: 2024-01-17)

主引用文献

Dos Santos Rodrigues, F.H.,Firczuk, H.,Breeze, A.L.,Cameron, A.D.,Walko, M.,Wilson, A.J.,Zanchin, N.I.T.,McCarthy, J.E.G.
The Leishmania PABP1-eIF4E4 interface: a novel 5'-3' interaction architecture for trans-spliced mRNAs.
Nucleic Acids Res., 47:1493-1504, 2019

PubMed Abstract: Trans-splicing of trypanosomatid polycistronic transcripts produces polyadenylated monocistronic mRNAs modified to form the 5' cap4 structure (m7Gpppm36,6,2'Apm2'Apm2'Cpm23,2'U). NMR and X-ray crystallography reveal that Leishmania has a unique type of N-terminally-extended cap-binding protein (eIF4E4) that binds via a PAM2 motif to PABP1. This relies on the interactions of a combination of polar and charged amino acid side-chains together with multiple hydrophobic interactions, and underpins a novel architecture in the Leishmania cap4-binding translation factor complex. Measurements using microscale thermophoresis, fluorescence anisotropy and surface plasmon resonance characterize the key interactions driving assembly of the Leishmania translation initiation complex. We demonstrate that this complex can accommodate Leishmania eIF4G3 which, unlike the standard eukaryotic initiation complex paradigm, binds tightly to eIF4E4, but not to PABP1. Thus, in Leishmania, the chain of interactions 5'cap4-eIF4E4-PABP1-poly(A) bridges the mRNA 5' and 3' ends. Exceptionally, therefore, by binding tightly to two protein ligands and to the mRNA 5' cap4 structure, the trypanosomatid N-terminally extended form of eIF4E acts as the core molecular scaffold for the mRNA-cap-binding complex. Finally, the eIF4E4 N-terminal extension is an intrinsically disordered region that transitions to a partly folded form upon binding to PABP1, whereby this interaction is not modulated by poly(A) binding to PABP1.

PubMed: 30476241
DOI: 10.1093/nar/gky1187

実験手法

X-RAY DIFFRACTION (1.89 Å)