6DZN

Pan-ebolavirus human antibody ADI-15878 Fab

Summary for 6DZN

• Entry DOI: 10.2210/pdb6dzn/pdb
• Descriptor: Antibody ADI-15878, light chain, Antibody ADI-15878, heavy chain, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: adi-15878, antibody, pan-ebolavirus, immunotherapeutic, ebola virus, bundibugyo virus, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 47658.58

Authors

Murin, C.D.,Ward, A.B.,Bruhn, J.F.,Stanfield, R. (deposition date: 2018-07-05, release date: 2018-09-12, Last modification date: 2024-10-23)

Primary citation

Murin, C.D.,Bruhn, J.F.,Bornholdt, Z.A.,Copps, J.,Stanfield, R.,Ward, A.B.
Structural Basis of Pan-Ebolavirus Neutralization by an Antibody Targeting the Glycoprotein Fusion Loop.
Cell Rep, 24:2723-2732.e4, 2018

PubMed Abstract: Monoclonal antibodies (mAbs) with pan-ebolavirus cross-reactivity are highly desirable, but development of such mAbs is limited by a lack of a molecular understanding of cross-reactive epitopes. The antibody ADI-15878 was previously identified from a human survivor of Ebola virus Makona variant (EBOV/Mak) infection. This mAb demonstrated potent neutralizing activity against all known ebolaviruses and provided protection in rodent and ferret models against three ebolavirus species. Here, we describe the unliganded crystal structure of ADI-15878 as well as the cryo-EM structures of ADI-15878 in complex with the EBOV/Mak and Bundibugyo virus (BDBV) glycoproteins (GPs). ADI-15878 binds through an induced-fit mechanism by targeting highly conserved residues in the internal fusion loop (IFL), bridging across GP protomers via the heptad repeat 1 (HR1) region. Our structures provide a more complete description of the ebolavirus immunogenic landscape, as well as a molecular basis for how rare but potent antibodies target conserved filoviral fusion machinery.

PubMed: 30184505
DOI: 10.1016/j.celrep.2018.08.009

Experimental method

X-RAY DIFFRACTION (2.1 Å)