5UQY

Crystal structure of Marburg virus GP in complex with the human survivor antibody MR78

Replaces:  3X2D

Summary for 5UQY

• Entry DOI: 10.2210/pdb5uqy/pdb
• Descriptor: ENVELOPE GLYCOPROTEIN GP1, alpha-D-mannopyranose, ENVELOPE GLYCOPROTEIN GP2, ... (10 entities in total)
• Functional Keywords: glycoprotein, viral protein, antibody, fab, viral protein-immune system complex, viral protein/immune system
• Biological source: Lake Victoria marburgvirus (strain Ravn-87) (MARV); More
• Total number of polymer chains: 16
• Total formula weight: 412484.12

Authors

Hashiguchi, T.,Fusco, M.L.,Hastie, K.M.,Bomholdt, Z.A.,Lee, J.E.,Flyak, A.I.,Matsuoka, R.,Kohda, D.,Yanagi, Y.,Hammel, M.,Crowe, J.E.,Saphire, E.O. (deposition date: 2017-02-08, release date: 2017-03-01, Last modification date: 2024-11-06)

Primary citation

Hashiguchi, T.,Fusco, M.L.,Bornholdt, Z.A.,Lee, J.E.,Flyak, A.I.,Matsuoka, R.,Kohda, D.,Yanagi, Y.,Hammel, M.,Crowe, J.E.,Saphire, E.O.
Structural basis for Marburg virus neutralization by a cross-reactive human antibody.
Cell, 160:904-912, 2015

PubMed 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.

PubMed: 25723165
DOI: 10.1016/j.cell.2015.01.041

Experimental method

X-RAY DIFFRACTION (3.6 Å)