Structure and self-assembly of the calcium binding matrix protein of human metapneumovirus

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-affi...

Full description

Bibliographic Details
Main Authors: Leyrat, C, Renner, M, Harlos, K, Huiskonen, J, Grimes, J
Format: Journal article
Published: 2014
_version_ 1826304217036357632
author Leyrat, C
Renner, M
Harlos, K
Huiskonen, J
Grimes, J
author_facet Leyrat, C
Renner, M
Harlos, K
Huiskonen, J
Grimes, J
author_sort Leyrat, C
collection OXFORD
description 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 Ca 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 Ca binding sites suggests a role for calcium in the replication and morphogenesis of pneumoviruses. © 2014 Elsevier Ltd All rights reserved.
first_indexed 2024-03-07T06:14:26Z
format Journal article
id oxford-uuid:f09a3774-8df2-4337-b1c2-0c4cb253e9bb
institution University of Oxford
last_indexed 2024-03-07T06:14:26Z
publishDate 2014
record_format dspace
spelling oxford-uuid:f09a3774-8df2-4337-b1c2-0c4cb253e9bb2022-03-27T11:49:22ZStructure and self-assembly of the calcium binding matrix protein of human metapneumovirusJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f09a3774-8df2-4337-b1c2-0c4cb253e9bbSymplectic Elements at Oxford2014Leyrat, CRenner, MHarlos, KHuiskonen, JGrimes, JThe 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 Ca 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 Ca binding sites suggests a role for calcium in the replication and morphogenesis of pneumoviruses. © 2014 Elsevier Ltd All rights reserved.
spellingShingle Leyrat, C
Renner, M
Harlos, K
Huiskonen, J
Grimes, J
Structure and self-assembly of the calcium binding matrix protein of human metapneumovirus
title Structure and self-assembly of the calcium binding matrix protein of human metapneumovirus
title_full Structure and self-assembly of the calcium binding matrix protein of human metapneumovirus
title_fullStr Structure and self-assembly of the calcium binding matrix protein of human metapneumovirus
title_full_unstemmed Structure and self-assembly of the calcium binding matrix protein of human metapneumovirus
title_short Structure and self-assembly of the calcium binding matrix protein of human metapneumovirus
title_sort structure and self assembly of the calcium binding matrix protein of human metapneumovirus
work_keys_str_mv AT leyratc structureandselfassemblyofthecalciumbindingmatrixproteinofhumanmetapneumovirus
AT rennerm structureandselfassemblyofthecalciumbindingmatrixproteinofhumanmetapneumovirus
AT harlosk structureandselfassemblyofthecalciumbindingmatrixproteinofhumanmetapneumovirus
AT huiskonenj structureandselfassemblyofthecalciumbindingmatrixproteinofhumanmetapneumovirus
AT grimesj structureandselfassemblyofthecalciumbindingmatrixproteinofhumanmetapneumovirus