5FHC

Crystal Structure of Protective Human Antibodies 100 and 114 in Complex with Ebola Virus Fusion Glycoprotein (GP)

Summary for 5FHC

• Entry DOI: 10.2210/pdb5fhc/pdb
• Related: 5FHA 5FHB
• Descriptor: Envelope glycoprotein, Envelope glycoprotein,Envelope glycoprotein, Antibody 100 Fab heavy chain, ... (6 entities in total)
• Functional Keywords: ig domain, fab, immune system, fusion, ebola virus, glycoprotein, gp, viral protein-immune system complex, viral protein/immune system
• Biological source: Zaire ebolavirus (strain Mayinga-76) (ZEBOV); More
• Cellular location: GP2: Virion membrane ; Single-pass type I membrane protein . GP1: Virion membrane ; Peripheral membrane protein. GP2-delta: Secreted : Q05320 Q05320
• Total number of polymer chains: 6
• Total formula weight: 139919.80

Authors

Gilman, M.S.A.,McLellan, J.S. (deposition date: 2015-12-21, release date: 2016-03-16, Last modification date: 2024-11-13)

Primary citation

Misasi, J.,Gilman, M.S.,Kanekiyo, M.,Gui, M.,Cagigi, A.,Mulangu, S.,Corti, D.,Ledgerwood, J.E.,Lanzavecchia, A.,Cunningham, J.,Muyembe-Tamfun, J.J.,Baxa, U.,Graham, B.S.,Xiang, Y.,Sullivan, N.J.,McLellan, J.S.
Structural and molecular basis for Ebola virus neutralization by protective human antibodies.
Science, 351:1343-1346, 2016

PubMed Abstract: Ebola virus causes hemorrhagic fever with a high case fatality rate for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman primates against all signs of Ebola virus disease, including viremia. Here, we demonstrate that mAb100 recognizes the base of the Ebola virus glycoprotein (GP) trimer, occludes access to the cathepsin-cleavage loop, and prevents the proteolytic cleavage of GP that is required for virus entry. We show that mAb114 interacts with the glycan cap and inner chalice of GP, remains associated after proteolytic removal of the glycan cap, and inhibits binding of cleaved GP to its receptor. These results define the basis of neutralization for two protective antibodies and may facilitate development of therapies and vaccines.

PubMed: 26917592
DOI: 10.1126/science.aad6117

Experimental method

X-RAY DIFFRACTION (6.704 Å)