Announcement

Collapse
No announcement yet.

Nat. Microb. Structural restrictions for influenza neuraminidase activity promote adaptation and diversification

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

  • Nat. Microb. Structural restrictions for influenza neuraminidase activity promote adaptation and diversification

    Nat Microbiol. 2019 Aug 26. doi: 10.1038/s41564-019-0537-z. [Epub ahead of print]
    Structural restrictions for influenza neuraminidase activity promote adaptation and diversification.

    Wang H1, Dou D1, ?stbye H1, Revol R1, Daniels R2,3.
    Author information

    1 Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden. 2 Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden. robertd@dbb.su.se. 3 Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. robertd@dbb.su.se.

    Abstract

    Influenza neuraminidase (NA) is a sialidase that contributes to viral mobility by removing the extracellular receptors for the haemagglutinin (HA) glycoprotein. However, it remains unclear why influenza NAs evolved to function as Ca2+-dependent tetramers that display variable stability. Here, we show that the Ca2+ ion located at the centre of the NA tetramer is a major stability determinant, as this Ca2+ ion is required for catalysis and its binding affinity varies between NAs. By examining NAs from 2009 pandemic-like H1N1 viruses, we traced the affinity variation to local substitutions that cause residues in the central Ca2+-binding pocket to reposition. A temporal analysis revealed that these local substitutions predictably alter the stability of the 2009 pandemic-like NAs and contribute to the tendency for the stability to vary up and down over time. In addition to the changes in stability, the structural plasticity of NA was also shown to support the formation of heterotetramers, which creates a mechanism for NA to obtain hybrid properties and propagate suboptimal mutants. Together, these results demonstrate how the structural restrictions for activity provide influenza NA with several mechanisms for adaptation and diversification.


    PMID: 31451775 DOI: 10.1038/s41564-019-0537-z

Working...
X