Using SAXS and NMR spectroscopy, we herein provide a high-resolutiondescription of the intrinsically disordered N-terminal domain (PNT, aa1–406) shared by the Nipah virus (NiV) phosphoprotein (P) and V protein,two key players in viral genome replication and in evasion of the hostinnate immune response, respectively. The use of multidimensional NMRspectroscopy allowed us to assign as much as 91% of the residues of thisintrinsically disordered domain whose size constitutes a technical challengefor NMR studies. Chemical shifts and nuclear relaxation measurementsprovide the picture of a highly flexible protein. The combination of SAXSand NMR information enabled the description of the conformationalensemble of the protein in solution. The present results, beyond providingan overall description of the conformational behavior of this intrinsicallydisordered region, also constitute an asset for obtaining atomisticinformation in future interaction studies with viral and/or cellular partners.The present study can thus be regarded as the starting point towards thedesign of inhibitors that by targeting crucial protein–protein interactionsinvolving PNT might be instrumental to combat this deadly virus.

Ensemble description of the intrinsically disordered N-terminal domain of the Nipah virus P/V protein from combined NMR and SAXS / Marco Schiavina, Edoardo Salladini, Maria Grazia Murrali, Giancarlo Tria, Isabella Caterina Felli, Roberta Pierattelli, Sonia Longhi. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - ELETTRONICO. - 10:(2020), pp. 0-0. [10.1038/s41598-020-76522-3]

Ensemble description of the intrinsically disordered N-terminal domain of the Nipah virus P/V protein from combined NMR and SAXS

Marco Schiavina;Maria Grazia Murrali;Giancarlo Tria;Isabella Caterina Felli
;
Roberta Pierattelli
;
2020

Abstract

Using SAXS and NMR spectroscopy, we herein provide a high-resolutiondescription of the intrinsically disordered N-terminal domain (PNT, aa1–406) shared by the Nipah virus (NiV) phosphoprotein (P) and V protein,two key players in viral genome replication and in evasion of the hostinnate immune response, respectively. The use of multidimensional NMRspectroscopy allowed us to assign as much as 91% of the residues of thisintrinsically disordered domain whose size constitutes a technical challengefor NMR studies. Chemical shifts and nuclear relaxation measurementsprovide the picture of a highly flexible protein. The combination of SAXSand NMR information enabled the description of the conformationalensemble of the protein in solution. The present results, beyond providingan overall description of the conformational behavior of this intrinsicallydisordered region, also constitute an asset for obtaining atomisticinformation in future interaction studies with viral and/or cellular partners.The present study can thus be regarded as the starting point towards thedesign of inhibitors that by targeting crucial protein–protein interactionsinvolving PNT might be instrumental to combat this deadly virus.
2020
10
0
0
Goal 3: Good health and well-being for people
Marco Schiavina, Edoardo Salladini, Maria Grazia Murrali, Giancarlo Tria, Isabella Caterina Felli, Roberta Pierattelli, Sonia Longhi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1214872
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