James Crowe
Faculty Member
Last active: 3/31/2019

Structural basis for Marburg virus neutralization by a cross-reactive human antibody.

Hashiguchi T, Fusco ML, Bornholdt ZA, Lee JE, Flyak AI, Matsuoka R, Kohda D, Yanagi Y, Hammel M, Crowe JE, Saphire EO
Cell. 2015 160 (5): 904-912

PMID: 25723165 · PMCID: PMC4344967 · DOI:10.1016/j.cell.2015.01.041

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.

Copyright © 2015 Elsevier Inc. All rights reserved.

MeSH Terms (20)

Amino Acid Sequence Animals Antibodies, Monoclonal Antibodies, Neutralizing Antibodies, Viral Antigen-Antibody Complex Cell Line Cross Reactions Crystallography, X-Ray Drosophila Ebolavirus Humans Immunoglobulin Fab Fragments Marburgvirus Marburg Virus Disease Models, Molecular Molecular Sequence Data Mucins Sequence Alignment Viral Envelope Proteins

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