title: Structure and self-assembly of the calcium binding matrix protein of human metapneumovirus.
abstract: 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.
authors: Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors: Cedric
authors: C
authors: Leyrat
authors: Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors: Max
authors: M
authors: Renner
authors: Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors: Karl
authors: K
authors: Harlos
authors: Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors: Juha T
authors: JT
authors: Huiskonen
authors: Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK; Diamond Light Source Limited, Harwell Science and Innovation Campus, Didcot, Oxfordshire, OX11 0DE, UK. Electronic address: jonathan@strubi.ox.ac.uk.
authors: Jonathan M
authors: JM
authors: Grimes
mesh_terms: D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D029121:Metapneumovirus / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D008854:Microscopy, Electron; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053838:Scattering, Small Angle; D013816:Thermodynamics; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D019065:Virus Assembly; D014779:Virus Replication; D014961:X-Ray Diffraction
chemical_list: D002135:Calcium-Binding Proteins; D010713:Phosphatidylcholines; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; C017251:1,2-oleoylphosphatidylcholine; D002118:Calcium