Structural Basis for Marburg Virus Neutralization by a Cross-Reactive Human Antibody

Takao Hashiguchi, Marnie L. Fusco, Zachary A. Bornholdt, Jeffrey E. Lee, Andrew I. Flyak, Rei Matsuoka, Daisuke Kohda, Yusuke Yanagi, Michal Hammel, James E. Crowe, Erica Ollmann Saphire

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Abstract

The filoviruses, including Marburg and Ebola, express a single glycoprotein on their surface, termed GP, which is responsible for attachment and entry of target cells. Filovirus GPs differ by up to 70% in protein sequence, and no antibodies are yet described that cross-react among them. Here, we present the 3.6 Å crystal structure of Marburg virus GP in complex with a cross-reactive antibody from a human survivor, and a lower resolution structure of the antibody bound to Ebola virus GP. The antibody, MR78, recognizes a GP1 epitope conserved across the filovirus family, which likely represents the binding site of their NPC1 receptor. Indeed, MR78 blocks binding of the essential NPC1 domain C. These structures and additional small-angle X-ray scattering of mucin-containing MARV and EBOV GPs suggest why such antibodies were not previously elicited in studies of Ebola virus, and provide critical templates for development of immunotherapeutics and inhibitors of entry.

Original languageEnglish
Pages (from-to)904-912
Number of pages9
JournalCell
Volume160
Issue number5
DOIs
Publication statusPublished - Feb 26 2015

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Marburgvirus
Viruses
Antibodies
Ebolavirus
Mucins
X ray scattering
Epitopes
Glycoproteins
Crystal structure
Binding Sites
X-Rays
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hashiguchi, T., Fusco, M. L., Bornholdt, Z. A., Lee, J. E., Flyak, A. I., Matsuoka, R., ... Saphire, E. O. (2015). Structural Basis for Marburg Virus Neutralization by a Cross-Reactive Human Antibody. Cell, 160(5), 904-912. https://doi.org/10.1016/j.cell.2015.01.041

Structural Basis for Marburg Virus Neutralization by a Cross-Reactive Human Antibody. / Hashiguchi, Takao; Fusco, Marnie L.; Bornholdt, Zachary A.; Lee, Jeffrey E.; Flyak, Andrew I.; Matsuoka, Rei; Kohda, Daisuke; Yanagi, Yusuke; Hammel, Michal; Crowe, James E.; Saphire, Erica Ollmann.

In: Cell, Vol. 160, No. 5, 26.02.2015, p. 904-912.

Research output: Contribution to journalArticle

Hashiguchi, T, Fusco, ML, Bornholdt, ZA, Lee, JE, Flyak, AI, Matsuoka, R, Kohda, D, Yanagi, Y, Hammel, M, Crowe, JE & Saphire, EO 2015, 'Structural Basis for Marburg Virus Neutralization by a Cross-Reactive Human Antibody', Cell, vol. 160, no. 5, pp. 904-912. https://doi.org/10.1016/j.cell.2015.01.041
Hashiguchi, Takao ; Fusco, Marnie L. ; Bornholdt, Zachary A. ; Lee, Jeffrey E. ; Flyak, Andrew I. ; Matsuoka, Rei ; Kohda, Daisuke ; Yanagi, Yusuke ; Hammel, Michal ; Crowe, James E. ; Saphire, Erica Ollmann. / Structural Basis for Marburg Virus Neutralization by a Cross-Reactive Human Antibody. In: Cell. 2015 ; Vol. 160, No. 5. pp. 904-912.
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