6XKI

Crystal structure of eIF4A-I in complex with RNA bound to des-MePateA, a pateamine A analog

6XKI の概要

• エントリーDOI: 10.2210/pdb6xki/pdb
• 分子名称: Eukaryotic initiation factor 4A-I, RNA (5'-R(*AP*GP*AP*GP*AP*GP*AP*GP*AP*G)-3'), PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (6 entities in total)
• 機能のキーワード: inhibitor, rna, translation initiation, translation, translation-rna-inhibitor complex, translation/rna/inhibitor
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48740.24

構造登録者

Liang, J.,Naineni, S.K.,Pelletier, J.,Nagar, B. (登録日: 2020-06-26, 公開日: 2021-01-06, 最終更新日: 2023-10-18)

主引用文献

Naineni, S.K.,Liang, J.,Hull, K.,Cencic, R.,Zhu, M.,Northcote, P.,Teesdale-Spittle, P.,Romo, D.,Nagar, B.,Pelletier, J.
Functional mimicry revealed by the crystal structure of an eIF4A:RNA complex bound to the interfacial inhibitor, desmethyl pateamine A.
Cell Chem Biol, 28:825-, 2021

PubMed Abstract: Interfacial inhibitors exert their biological effects through co-association with two macromolecules. The pateamine A (PatA) class of molecules function by stabilizing eukaryotic initiation factor (eIF) 4A RNA helicase onto RNA, resulting in translation initiation inhibition. Here, we present the crystal structure of an eIF4A1:RNA complex bound to an analog of the marine sponge-derived natural product PatA, C5-desmethyl PatA (DMPatA). One end of this small molecule wedges itself between two RNA bases while the other end is cradled by several protein residues. Strikingly, DMPatA interacts with the eIF4A1:RNA complex in an almost identical fashion as rocaglamide A (RocA), despite being completely unrelated from a structural standpoint. The structural data rationalize the ability of PatA analogs to target a wider range of RNA substrates compared to RocA. We define the molecular basis of how DMPatA is able to clamp eIF4A1 onto RNA, imparting potent inhibitory properties to this molecule.

PubMed: 33412110
DOI: 10.1016/j.chembiol.2020.12.006

実験手法

X-RAY DIFFRACTION (2.87 Å)