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Structural basis for Marburg virus neutralization by a cross-reactive human antibody.
- Source :
-
Cell [Cell] 2015 Feb 26; Vol. 160 (5), pp. 904-912. - Publication Year :
- 2015
-
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.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Animals
Antibodies, Monoclonal chemistry
Antibodies, Monoclonal metabolism
Antibodies, Neutralizing isolation & purification
Antibodies, Neutralizing metabolism
Antibodies, Viral chemistry
Antibodies, Viral immunology
Antibodies, Viral metabolism
Antigen-Antibody Complex chemistry
Cell Line
Cross Reactions
Crystallography, X-Ray
Drosophila
Ebolavirus chemistry
Humans
Immunoglobulin Fab Fragments chemistry
Immunoglobulin Fab Fragments metabolism
Marburg Virus Disease immunology
Marburgvirus genetics
Marburgvirus immunology
Models, Molecular
Molecular Sequence Data
Mucins chemistry
Sequence Alignment
Viral Envelope Proteins metabolism
Antibodies, Neutralizing chemistry
Antibodies, Neutralizing immunology
Marburgvirus chemistry
Viral Envelope Proteins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 160
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 25723165
- Full Text :
- https://doi.org/10.1016/j.cell.2015.01.041