5WB0

Crystal structure of human metapneumovirus fusion glycoprotein stabilized in the prefusion state

Summary for 5WB0

• Entry DOI: 10.2210/pdb5wb0/pdb
• Descriptor: Fusion glycoprotein F0, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: class i viral fusion protein, fusion, metapneumovirus, prefusion, viral protein
• Biological source: Human metapneumovirus
• Total number of polymer chains: 1
• Total formula weight: 61110.84

Authors

Battles, M.B.,McLellan, J.S. (deposition date: 2017-06-27, release date: 2017-11-22, Last modification date: 2024-11-13)

Primary citation

Battles, M.B.,Mas, V.,Olmedillas, E.,Cano, O.,Vazquez, M.,Rodriguez, L.,Melero, J.A.,McLellan, J.S.
Structure and immunogenicity of pre-fusion-stabilized human metapneumovirus F glycoprotein.
Nat Commun, 8:1528-1528, 2017

PubMed Abstract: Human metapneumovirus (hMPV) is a frequent cause of bronchiolitis in young children. Its F glycoprotein mediates virus-cell membrane fusion and is the primary target of neutralizing antibodies. The inability to produce recombinant hMPV F glycoprotein in the metastable pre-fusion conformation has hindered structural and immunological studies. Here, we engineer a pre-fusion-stabilized hMPV F ectodomain and determine its crystal structure to 2.6 Å resolution. This structure reveals molecular determinants of strain-dependent acid-induced fusion, as well as insights into refolding from pre- to post-fusion conformations. A dense glycan shield at the apex of pre-fusion hMPV F suggests that antibodies against this site may not be elicited by host immune responses, which is confirmed by depletion studies of human immunoglobulins and by mouse immunizations. This is a major difference with pre-fusion F from human respiratory syncytial virus (hRSV), and collectively our results should facilitate development of effective hMPV vaccine candidates.

PubMed: 29142300
DOI: 10.1038/s41467-017-01708-9

Experimental method

X-RAY DIFFRACTION (2.601 Å)