2L9J
hRSV M2-1 core domain structure
Summary for 2L9J
| Entry DOI | 10.2210/pdb2l9j/pdb |
| NMR Information | BMRB: 17451 |
| Descriptor | Matrix protein 2-1 (1 entity in total) |
| Functional Keywords | processivity, transcription co-factor, viral protein, rna binding protein, respiratory syncytial virus (rsv), transcription |
| Biological source | Human respiratory syncytial virus |
| Total number of polymer chains | 1 |
| Total formula weight | 13514.42 |
| Authors | Dubosclard, V.,Blondot, M.,Bontems, F.,Eleouet, J.,Sizun, C. (deposition date: 2011-02-12, release date: 2012-02-15, Last modification date: 2024-05-15) |
| Primary citation | 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 Cited by 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: 22675274DOI: 10.1371/journal.ppat.1002734 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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