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Structure of Protein M2-1 from HMPV

3D Structure

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Functional Information

The M2-1 protein is a zinc binding protein encoded by the Human Metapneumovirus (hMPV) that plays a vital role in RNA synthesis regulation. M2-1 is a basic protein with 187 amino acids and a theoretical pl of 9.14. It is expressed only during the viral cycle's replication. M2-1 recruits the antitermination factor to the polymerase during transcription to bind nascent viral mRNA. Zinc binding activity is essential for viral replication and pathogenesis in vivo. (PubMed:15890897)

Interactions

The homotetramer interacts with RNA. Interacts with the phosphoprotein (P); this interaction is required for protein M2- 1 function, localization in host inclusion bodies. Interacts with the nucleoprotein (N). Interacts with the matrix protein (M); this interaction directs M localization to cytoplasmic inclusions comprising viral proteins L, N, P, and M2-1 and mediates M association with the nucleocapsid.

Domains Orgainzation

  • Zinc Finger = 1-28.
  • Oligomerization domain=32-49.
  • Central globular core = 75-167.

Mutation

  • C7S = 58% loss of zinc binding and loss of homotetramerization. Delayed viral replication.
  • C15S = 58% loss of zinc binding and loss of homotetramerization. Delayed viral replication.
  • C21S = Complete loss of zinc binding and loss of homotetramerization. Delayed viral replication.
  • C25S = Complete loss of zinc binding and loss of homotetramerization. Delayed viral replication.

Essential Residues

Residues such as Lys8, Phe23, Lys91 and Arg149 are involved in RNA binding.

Post-translational Modification

Serine 57 and 60 are phosphorylated by the host.