8T2A

Crystal structure of SCV PTE G18A mutant RNA in complex with Fab BL3-6

8T2A の概要

• エントリーDOI: 10.2210/pdb8t2a/pdb
• 分子名称: RNA (90-MER), BL3-6 Fab heavy chain, BL3-6 Fab light chain (3 entities in total)
• 機能のキーワード: viral rna, fab, translation, 3'cite, rna, rna-immune system complex, rna/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 77310.92

構造登録者

Ojha, M.,Koirala, D. (登録日: 2023-06-05, 公開日: 2024-01-10, 最終更新日: 2024-10-16)

主引用文献

Ojha, M.,Vogt, J.,Das, N.K.,Redmond, E.,Singh, K.,Banna, H.A.,Sadat, T.,Koirala, D.
Structure of saguaro cactus virus 3' translational enhancer mimics 5' cap for eIF4E binding.
Proc.Natl.Acad.Sci.USA, 121:e2313677121-e2313677121, 2024

PubMed Abstract: The genomes of several plant viruses contain RNA structures at their 3' ends called cap-independent translation enhancers (CITEs) that bind the host protein factors such as mRNA 5' cap-binding protein eIF4E for promoting cap-independent genome translation. However, the structural basis of such 5' cap-binding protein recognition by the uncapped RNA remains largely unknown. Here, we have determined the crystal structure of a 3' CITE, panicum mosaic virus-like translation enhancer (PTE) from the saguaro cactus virus (SCV), using a Fab crystallization chaperone. The PTE RNA folds into a three-way junction architecture with a pseudoknot between the purine-rich R domain and pyrimidine-rich Y domain, which organizes the overall structure to protrude out a specific guanine nucleotide, G18, from the R domain that comprises a major interaction site for the eIF4E binding. The superimposable crystal structures of the wild-type, G18A, G18C, and G18U mutants suggest that the PTE scaffold is preorganized with the flipped-out G18 ready to dock into the eIF4E 5' cap-binding pocket. The binding studies with wheat and human eIF4Es using gel electrophoresis and isothermal titration calorimetry, and molecular docking computation for the PTE-eIF4E complex demonstrated that the PTE structure essentially mimics the mRNA 5' cap for eIF4E binding. Such 5' cap mimicry by the uncapped and structured viral RNA highlights how viruses can exploit RNA structures to mimic the host protein-binding partners and bypass the canonical mechanisms for their genome translation, providing opportunities for a better understanding of virus-host interactions and non-canonical translation mechanisms found in many pathogenic RNA viruses.

PubMed: 38241435
DOI: 10.1073/pnas.2313677121

実験手法

X-RAY DIFFRACTION (3.17 Å)