5L1X

Structure of the Human Metapneumovirus Fusion Protein in the Postfusion Conformation

Summary for 5L1X

• Entry DOI: 10.2210/pdb5l1x/pdb
• Descriptor: hMPV F2 subunit, hMPV F1 subunit, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: class i fusion protein, viral protein
• Biological source: Human metapneumovirus; More
• Total number of polymer chains: 12
• Total formula weight: 318179.93

Authors

Mas, V.,Melero, J.A.,McLellan, J.S. (deposition date: 2016-07-29, release date: 2016-08-24, Last modification date: 2024-10-23)

Primary citation

Mas, V.,Rodriguez, L.,Olmedillas, E.,Cano, O.,Palomo, C.,Terron, M.C.,Luque, D.,Melero, J.A.,McLellan, J.S.
Engineering, Structure and Immunogenicity of the Human Metapneumovirus F Protein in the Postfusion Conformation.
Plos Pathog., 12:e1005859-e1005859, 2016

PubMed 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 Å 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.

PubMed: 27611367
DOI: 10.1371/journal.ppat.1005859

Experimental method

X-RAY DIFFRACTION (3.3 Å)