Journal
ONCOTARGET
Volume 8, Issue 47, Pages 82446-82458Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.19401
Keywords
ningnanmycin; TMV CP; binding analysis; interaction studies
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Funding
- National Natural Science Foundation of China [21132003, 31460460, 21502032]
- Subsidy Project for Outstanding Key Laboratory of Guizhou Province in China [20154004]
- Provincial University Cooperation Plan of Guizhou Province in China [20147001]
- Collaborative Innovation Center for Natural Products and Biological Drugs of Yunnan
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Tobacco mosaic virus (TMV) causes severe plant diseases worldwide; however, effective antiviral agents for controlling TMV infections are not available. This lack of effective antiviral agents is mainly due to the poor understanding of potential targets associated with TMV infections. During infection, the coat protein (CP), which is delivered by viral particles into susceptible host cells, provides protection for viral RNA. Here, we found that Ningnanmycin (NNM), a commercially used plant antibacterial agent, inhibits the assembly of the CP by directly binding several residues. These interactions cause the disassembly of the CP from discs into monomers, leading to an almost complete loss of pathogenicity. Substitutions in the involved binding residues resulted in mutants that were significantly less sensitive to NNM. Thus, targeting the binding of viral CPs through small molecular agents offers an effective strategy to study the mechanism of NNM.
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