Structure and Self-Assembly of the Calcium Binding Matrix Protein of Human Metapneumovirus

نویسندگان

  • Cedric Leyrat
  • Max Renner
  • Karl Harlos
  • Juha T. Huiskonen
  • Jonathan M. Grimes
چکیده

The matrix protein (M) of paramyxoviruses plays a key role in determining virion morphology by directing viral assembly and budding. Here, we report the crystal structure of the human metapneumovirus M at 2.8 Å resolution in its native dimeric state. The structure reveals the presence of a high-affinity Ca²⁺ binding site. Molecular dynamics simulations (MDS) predict a secondary lower-affinity site that correlates well with data from fluorescence-based thermal shift assays. By combining small-angle X-ray scattering with MDS and ensemble analysis, we captured the structure and dynamics of M in solution. Our analysis reveals a large positively charged patch on the protein surface that is involved in membrane interaction. Structural analysis of DOPC-induced polymerization of M into helical filaments using electron microscopy leads to a model of M self-assembly. The conservation of the Ca²⁺ binding sites suggests a role for calcium in the replication and morphogenesis of pneumoviruses.

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عنوان ژورنال:

دوره 22  شماره 

صفحات  -

تاریخ انتشار 2014