The U4 antibody epitope on human papillomavirus 16 identified by cryo-electron microscopy

Jian Guan, Stephanie M. Bywaters, Sarah A. Brendle, Hyunwook Lee, Robert E. Ashley, Neil D. Christensen, Susan Hafenstein

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The human papillomavirus (HPV) major structural protein L1 composes capsomers that are linked together through interactions mediated by the L1 C terminus to constitute a T=7 icosahedral capsid. H16.U4 is a type-specific monoclonal antibody recognizing a conformation-dependent neutralizing epitope of HPV thought to include the L1 protein C terminus. The structure of human papillomavirus 16 (HPV16) complexed with H16.U4 fragments of antibody (Fab) was solved by cryo-electron microscopy (cryo-EM) image reconstruction. Atomic structures of virus and Fab were fitted into the corresponding cryo-EM densities to identify the antigenic epitope. The antibody footprint mapped predominately to the L1 C-terminal arm with an additional contact point on the side of the capsomer. This footprint describes an epitope that is presented capsid-wide. However, although the H16.U4 epitope suggests the presence of 360 potential binding sites exposed in the capsid valley between each capsomer, H16.U4 Fab bound only to epitopes located around the icosahedral five-fold vertex of the capsid. Thus, the binding characteristics of H16.U4 defined in this study showed a distinctive selectivity for local conformation-dependent interactions with specific L1 invading arms between five-fold related capsomers.

Original languageEnglish (US)
Pages (from-to)12108-12117
Number of pages10
JournalJournal of virology
Volume89
Issue number23
DOIs
StatePublished - Jan 1 2015

Fingerprint

Human papillomavirus 16
Cryoelectron Microscopy
capsid
epitopes
Capsid
Epitopes
Immunoglobulin Fragments
antibodies
Antibodies
Papillomaviridae
viral morphology
Viral Structures
Computer-Assisted Image Processing
structural proteins
Protein C
neutralization
binding sites
monoclonal antibodies
valleys
Binding Sites

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Guan, Jian ; Bywaters, Stephanie M. ; Brendle, Sarah A. ; Lee, Hyunwook ; Ashley, Robert E. ; Christensen, Neil D. ; Hafenstein, Susan. / The U4 antibody epitope on human papillomavirus 16 identified by cryo-electron microscopy. In: Journal of virology. 2015 ; Vol. 89, No. 23. pp. 12108-12117.
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The U4 antibody epitope on human papillomavirus 16 identified by cryo-electron microscopy. / Guan, Jian; Bywaters, Stephanie M.; Brendle, Sarah A.; Lee, Hyunwook; Ashley, Robert E.; Christensen, Neil D.; Hafenstein, Susan.

In: Journal of virology, Vol. 89, No. 23, 01.01.2015, p. 12108-12117.

Research output: Contribution to journalArticle

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