2L9J

hRSV M2-1 core domain structure

2L9J の概要

• エントリーDOI: 10.2210/pdb2l9j/pdb
• NMR情報: BMRB: 17451
• 分子名称: Matrix protein 2-1 (1 entity in total)
• 機能のキーワード: processivity, transcription co-factor, viral protein, rna binding protein, respiratory syncytial virus (rsv), transcription
• 由来する生物種: Human respiratory syncytial virus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13514.42

構造登録者

Dubosclard, V.,Blondot, M.,Bontems, F.,Eleouet, J.,Sizun, C. (登録日: 2011-02-12, 公開日: 2012-02-15, 最終更新日: 2024-05-15)

主引用文献

Blondot, M.L.,Dubosclard, V.,Fix, J.,Lassoued, S.,Aumont-Nicaise, M.,Bontems, F.,Eleouet, J.F.,Sizun, C.
Structure and functional analysis of the RNA- and viral phosphoprotein-binding domain of respiratory syncytial virus M2-1 protein.
Plos Pathog., 8:e1002734-e1002734, 2012

PubMed Abstract: Respiratory syncytial virus (RSV) protein M2-1 functions as an essential transcriptional cofactor of the viral RNA-dependent RNA polymerase (RdRp) complex by increasing polymerase processivity. M2-1 is a modular RNA binding protein that also interacts with the viral phosphoprotein P, another component of the RdRp complex. These binding properties are related to the core region of M2-1 encompassing residues S58 to K177. Here we report the NMR structure of the RSV M2-1(58-177) core domain, which is structurally homologous to the C-terminal domain of Ebola virus VP30, a transcription co-factor sharing functional similarity with M2-1. The partial overlap of RNA and P interaction surfaces on M2-1(58-177), as determined by NMR, rationalizes the previously observed competitive behavior of RNA versus P. Using site-directed mutagenesis, we identified eight residues located on these surfaces that are critical for an efficient transcription activity of the RdRp complex. Single mutations of these residues disrupted specifically either P or RNA binding to M2-1 in vitro. M2-1 recruitment to cytoplasmic inclusion bodies, which are regarded as sites of viral RNA synthesis, was impaired by mutations affecting only binding to P, but not to RNA, suggesting that M2-1 is associated to the holonucleocapsid by interacting with P. These results reveal that RNA and P binding to M2-1 can be uncoupled and that both are critical for the transcriptional antitermination function of M2-1.

PubMed: 22675274
DOI: 10.1371/journal.ppat.1002734

実験手法

SOLUTION NMR