6xki

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

Structural highlights

6xki is a 2 chain structure with sequence from Mus musculus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.87Å
Ligands:ANP, MG, V6D
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IF4A1_MOUSE ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon.

Publication Abstract from PubMed

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.

Functional mimicry revealed by the crystal structure of an eIF4A:RNA complex bound to the interfacial inhibitor, desmethyl pateamine A.,Naineni SK, Liang J, Hull K, Cencic R, Zhu M, Northcote P, Teesdale-Spittle P, Romo D, Nagar B, Pelletier J Cell Chem Biol. 2021 Jun 17;28(6):825-834.e6. doi: , 10.1016/j.chembiol.2020.12.006. Epub 2021 Jan 6. PMID:33412110[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
2 reviews cite this structure
Cellular functions of eukaryotic RNA helicases and their links to human diseases.
Bohnsack et al. (2023)
1 more
9 other articles
No citations found

See Also

References

  1. ↑ Naineni SK, 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. 2021 Jun 17;28(6):825-834.e6. PMID:33412110 doi:10.1016/j.chembiol.2020.12.006

Contents


PDB ID 6xki

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OCA

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