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6MAM

Cleaved Ebola GP in complex with a broadly neutralizing human antibody, ADI-15946

Summary for 6MAM
Entry DOI10.2210/pdb6mam/pdb
DescriptorADI-15946 Fab Heavy Chain, ADI-15946 Fab Light Chain, Envelope glycoprotein, ... (6 entities in total)
Functional Keywordsebola, ebolavirus, antibody, mab, fab, gp, glycoprotein, cleaved, monoclonal, broad, filovirus, marburg, ebov, bdbv, sudv, restv, tafv, marv, ravv, bundibugyo, sudan, human, viral protein, viral protein-immune system complex, viral protein/immune system
Biological sourceHomo sapiens (Human)
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Total number of polymer chains12
Total formula weight264472.51
Authors
West, B.R.,Moyer, C.L.,Fusco, M.L.,Saphire, E.O. (deposition date: 2018-08-28, release date: 2019-03-20, Last modification date: 2024-11-20)
Primary citationWest, B.R.,Wec, A.Z.,Moyer, C.L.,Fusco, M.L.,Ilinykh, P.A.,Huang, K.,Wirchnianski, A.S.,James, R.M.,Herbert, A.S.,Hui, S.,Goodwin, E.,Howell, K.A.,Kailasan, S.,Aman, M.J.,Walker, L.M.,Dye, J.M.,Bukreyev, A.,Chandran, K.,Saphire, E.O.
Structural basis of broad ebolavirus neutralization by a human survivor antibody.
Nat. Struct. Mol. Biol., 26:204-212, 2019
Cited by
PubMed Abstract: The structural features that govern broad-spectrum activity of broadly neutralizing anti-ebolavirus antibodies (Abs) outside of the internal fusion loop epitope are currently unknown. Here we describe the structure of a broadly neutralizing human monoclonal Ab (mAb), ADI-15946, which was identified in a human survivor of the 2013-2016 outbreak. The crystal structure of ADI-15946 in complex with cleaved Ebola virus glycoprotein (EBOV GP) reveals that binding of the mAb structurally mimics the conserved interaction between the EBOV GP core and its glycan cap β17-β18 loop to inhibit infection. Both endosomal proteolysis of EBOV GP and binding of mAb FVM09 displace this loop, thereby increasing exposure of ADI-15946's conserved epitope and enhancing neutralization. Our work also mapped the paratope of ADI-15946, thereby explaining reduced activity against Sudan virus, which enabled rational, structure-guided engineering to enhance binding and neutralization of Sudan virus while retaining the parental activity against EBOV and Bundibugyo virus.
PubMed: 30833785
DOI: 10.1038/s41594-019-0191-4
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (4.1 Å)
Structure validation

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