5L1X: Structure Of The Human Metapneumovirus Fusion Protein In The Postfusion Conformation

Citation:
Abstract
Human metapneumovirus (hMPV) is a paramyxovirus that is a common cause of bronchiolitis and pneumonia in children less than five years of age. The hMPV fusion (F) glycoprotein is the primary target of neutralizing antibodies and is thus a critical vaccine antigen. To facilitate structure-based vaccine design, we stabilized the ectodomain of the hMPV F protein in the postfusion conformation and determined its structure to a resolution of 3.3 A by X-ray crystallography. The structure resembles an elongated cone and is very similar to the postfusion F protein from the related human respiratory syncytial virus (hRSV). In contrast, significant differences were apparent with the postfusion F proteins from other paramyxoviruses, such as human parainfluenza type 3 (hPIV3) and Newcastle disease virus (NDV). The high similarity of hMPV and hRSV postfusion F in two antigenic sites targeted by neutralizing antibodies prompted us to test for antibody cross-reactivity. The widely used monoclonal antibody 101F, which binds to antigenic site IV of hRSV F, was found to cross-react with hMPV postfusion F and neutralize both hRSV and hMPV. Despite the cross-reactivity of 101F and the reported cross-reactivity of two other antibodies, 54G10 and MPE8, we found no detectable cross-reactivity in the polyclonal antibody responses raised in mice against the postfusion forms of either hMPV or hRSV F. The postfusion-stabilized hMPV F protein did, however, elicit high titers of hMPV-neutralizing activity, suggesting that it could serve as an effective subunit vaccine. Structural insights from these studies should be useful for designing novel immunogens able to induce wider cross-reactive antibody responses.
PDB ID: 5L1XDownload
MMDB ID: 142336
PDB Deposition Date: 2016/7/29
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 3.3  Å
Source Organism:
Similar Structures:
Biological Unit for 5L1X: hexameric; determined by author and by software (PISA)
Molecular Components in 5L1X
Label Count Molecule
Proteins (6 molecules)
3
Hmpv F2 Subunit
Molecule annotation
3
Hmpv F1 Subunit
Molecule annotation
Chemicals (12 molecules)
1
6
2
3
3
3
* Click molecule labels to explore molecular sequence information.

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