tetano
Editor, Senior Moderator
Structure. 2014 Feb 25. pii: S0969-2126(14)00038-0. doi: 10.1016/j.str.2014.01.010. [Epub ahead of print]
19F NMR Reveals Multiple Conformations at the Dimer Interface of the Nonstructural Protein 1 Effector Domain from Influenza A Virus.
Aramini JM1, Hamilton K2, Ma LC2, Swapna GV2, Leonard PG3, Ladbury JE3, Krug RM4, Montelione GT5.
Author information
Abstract
Nonstructural protein 1 of influenza A virus (NS1A) is a conserved virulence factor comprised of an N-terminal double-stranded RNA (dsRNA)-binding domain and a multifunctional C-terminal effector domain (ED), each of which can independently form symmetric homodimers. Here we apply 19F NMR to NS1A from influenza A/Udorn/307/1972 virus (H3N2) labeled with 5-fluorotryptophan, and we demonstrate that the 19F signal of Trp187 is a sensitive, direct monitor of the ED helix:helix dimer interface. 19F relaxation dispersion data reveal the presence of conformational dynamics within this functionally important protein
rotein interface, whose rate is more than three orders of magnitude faster than the kinetics of ED dimerization. 19F NMR also affords direct spectroscopic evidence that Trp187, which mediates intermolecular ED:ED interactions required for cooperative dsRNA binding, is solvent exposed in full-length NS1A at concentrations below aggregation. These results have important implications for the diverse roles of this NS1A epitope during influenza virus infection.
Copyright ? 2014 Elsevier Ltd. All rights reserved.
PMID:
24582435
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24582435
19F NMR Reveals Multiple Conformations at the Dimer Interface of the Nonstructural Protein 1 Effector Domain from Influenza A Virus.
Aramini JM1, Hamilton K2, Ma LC2, Swapna GV2, Leonard PG3, Ladbury JE3, Krug RM4, Montelione GT5.
Author information
Abstract
Nonstructural protein 1 of influenza A virus (NS1A) is a conserved virulence factor comprised of an N-terminal double-stranded RNA (dsRNA)-binding domain and a multifunctional C-terminal effector domain (ED), each of which can independently form symmetric homodimers. Here we apply 19F NMR to NS1A from influenza A/Udorn/307/1972 virus (H3N2) labeled with 5-fluorotryptophan, and we demonstrate that the 19F signal of Trp187 is a sensitive, direct monitor of the ED helix:helix dimer interface. 19F relaxation dispersion data reveal the presence of conformational dynamics within this functionally important protein
rotein interface, whose rate is more than three orders of magnitude faster than the kinetics of ED dimerization. 19F NMR also affords direct spectroscopic evidence that Trp187, which mediates intermolecular ED:ED interactions required for cooperative dsRNA binding, is solvent exposed in full-length NS1A at concentrations below aggregation. These results have important implications for the diverse roles of this NS1A epitope during influenza virus infection.Copyright ? 2014 Elsevier Ltd. All rights reserved.
PMID:
24582435
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24582435