7TL0

Cryo-EM structure of hMPV preF bound by Fabs MPE8 and SAN32-2

Summary for 7TL0

• Entry DOI: 10.2210/pdb7tl0/pdb
• Related: 7TJQ
• EMDB information: 25929 25982
• Descriptor: Fusion glycoprotein F0, SAN32-2 Fab heavy chain, SAN32-2 Fab light chain, ... (7 entities in total)
• Functional Keywords: neutralizing antibody, fusion protein, metapneumovirus, site 0, viral protein-immune system complex, viral protein/immune system
• Biological source: Human metapneumovirus; More
• Total number of polymer chains: 15
• Total formula weight: 467161.72

Authors

Rush, S.A.,Hsieh, C.-L.,McLellan, J.S. (deposition date: 2022-01-17, release date: 2022-09-14, Last modification date: 2025-05-21)

Primary citation

Rush, S.A.,Brar, G.,Hsieh, C.L.,Chautard, E.,Rainho-Tomko, J.N.,Slade, C.D.,Bricault, C.A.,Kume, A.,Kearns, J.,Groppo, R.,Mundle, S.T.,Zhang, L.,Casimiro, D.,Fu, T.M.,DiNapoli, J.M.,McLellan, J.S.
Characterization of prefusion-F-specific antibodies elicited by natural infection with human metapneumovirus.
Cell Rep, 40:111399-111399, 2022

PubMed Abstract: Human metapneumovirus (hMPV) is a major cause of acute respiratory infections in infants and older adults, for which no vaccines or therapeutics are available. The viral fusion (F) glycoprotein is required for entry and is the primary target of neutralizing antibodies; however, little is known about the humoral immune response generated from natural infection. Here, using prefusion-stabilized F proteins to interrogate memory B cells from two older adults, we obtain over 700 paired non-IgM antibody sequences representing 563 clonotypes, indicative of a highly polyclonal response. Characterization of 136 monoclonal antibodies reveals broad recognition of the protein surface, with potently neutralizing antibodies targeting each antigenic site. Cryo-EM studies further reveal two non-canonical sites and the molecular basis for recognition of the apex of hMPV F by two prefusion-specific neutralizing antibodies. Collectively, these results provide insight into the humoral response to hMPV infection in older adults and will help guide vaccine development.

PubMed: 36130517
DOI: 10.1016/j.celrep.2022.111399

Experimental method

ELECTRON MICROSCOPY (3.06 Å)