3J7E

Electron cryo-microscopy of human papillomavirus 16 and H16.V5 Fab fragments

Summary for 3J7E

• Entry DOI: 10.2210/pdb3j7e/pdb
• Related: 3J7G
• EMDB information: 5991 5992 5993 5994
• Descriptor: H16.V5 Fab light chain, H16.V5 Fab heavy chain (2 entities in total)
• Functional Keywords: hpv16.v5 fab variable domain, hi and fg loops, hpv16 capsid, virus-fab complex, neutralization antibody, maturation, immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 8
• Total formula weight: 104484.52

Authors

Lee, H.,Brendle, S.A.,Bywaters, S.M.,Christensen, N.D.,Hafenstein, S. (deposition date: 2014-06-23, release date: 2014-11-26, Last modification date: 2024-11-27)

Primary citation

Lee, H.,Brendle, S.A.,Bywaters, S.M.,Guan, J.,Ashley, R.E.,Yoder, J.D.,Makhov, A.M.,Conway, J.F.,Christensen, N.D.,Hafenstein, S.
A cryo-electron microscopy study identifies the complete H16.V5 epitope and reveals global conformational changes initiated by binding of the neutralizing antibody fragment.
J.Virol., 89:1428-1438, 2015

PubMed Abstract: Human papillomavirus 16 (HPV16) is a worldwide health threat and an etiologic agent of cervical cancer. To understand the antigenic properties of HPV16, we pursued a structural study to elucidate HPV capsids and antibody interactions. The cryo-electron microscopy (cryo-EM) structures of a mature HPV16 particle and an altered capsid particle were solved individually and as complexes with fragment of antibody (Fab) from the neutralizing antibody H16.V5. Fitted crystal structures provided a pseudoatomic model of the virus-Fab complex, which identified a precise footprint of H16.V5, including previously unrecognized residues. The altered-capsid-Fab complex map showed that binding of the Fab induced significant conformational changes that were not seen in the altered-capsid structure alone. These changes included more ordered surface loops, consolidated so-called "invading-arm" structures, and tighter intercapsomeric connections at the capsid floor. The H16.V5 Fab preferentially bound hexavalent capsomers likely with a stabilizing effect that directly correlated with the number of bound Fabs. Additional cryo-EM reconstructions of the virus-Fab complex for different incubation times and structural analysis provide a model for a hyperstabilization of the capsomer by H16.V5 Fab and showed that the Fab distinguishes subtle differences between antigenic sites.

PubMed: 25392224
DOI: 10.1128/JVI.02898-14

Experimental method

ELECTRON MICROSCOPY (13.6 Å)