PMID- 30184505
OWN - NLM
STAT- MEDLINE
DCOM- 20191125
LR  - 20191125
IS  - 2211-1247 (Electronic)
VI  - 24
IP  - 10
DP  - 2018 Sep 4
TI  - Structural Basis of Pan-Ebolavirus Neutralization by an Antibody Targeting the 
      Glycoprotein Fusion Loop.
PG  - 2723-2732.e4
LID - S2211-1247(18)31263-4 [pii]
LID - 10.1016/j.celrep.2018.08.009 [doi]
AB  - 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.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Murin, Charles D
AU  - Murin CD
AD  - Department of Integrative Structural and Computational Biology, The Scripps 
      Research Institute, La Jolla, CA 92037, USA.
FAU - Bruhn, Jessica F
AU  - Bruhn JF
AD  - Laboratory of Genetics and Helmsley Center for Genomic Medicine, The Salk 
      Institute for Biological Sciences, La Jolla, CA 92037, USA.
FAU - Bornholdt, Zachary A
AU  - Bornholdt ZA
AD  - Mapp Biopharmaceutical, San Diego, CA 92121, USA.
FAU - Copps, Jeffrey
AU  - Copps J
AD  - Department of Integrative Structural and Computational Biology, The Scripps 
      Research Institute, La Jolla, CA 92037, USA.
FAU - Stanfield, Robyn
AU  - Stanfield R
AD  - Department of Integrative Structural and Computational Biology, The Scripps 
      Research Institute, La Jolla, CA 92037, USA.
FAU - Ward, Andrew B
AU  - Ward AB
AD  - Department of Integrative Structural and Computational Biology, The Scripps 
      Research Institute, La Jolla, CA 92037, USA. Electronic address: 
      andrew@scripps.edu.
LA  - eng
GR  - U19 AI109762/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Glycoproteins)
SB  - IM
MH  - Antibodies, Neutralizing/genetics/immunology/*metabolism
MH  - Antibodies, Viral/immunology/metabolism
MH  - Cryoelectron Microscopy
MH  - Crystallography
MH  - Ebolavirus/genetics/*metabolism
MH  - Filoviridae/genetics/*metabolism
MH  - Glycoproteins/genetics/*immunology/*metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Structure, Secondary
PMC - PMC6174886
MID - NIHMS1506728
OTO - NOTNLM
OT  - Bundibugyo virus
OT  - Ebola virus
OT  - antibody
OT  - filovirus
OT  - glycoprotein
OT  - pan-filoviral
COIS- DECLARATION OF INTERESTS The authors declare no competing interests.
EDAT- 2018/09/06 06:00
MHDA- 2019/11/26 06:00
PMCR- 2018/10/08
CRDT- 2018/09/06 06:00
PHST- 2018/05/14 00:00 [received]
PHST- 2018/07/11 00:00 [revised]
PHST- 2018/08/06 00:00 [accepted]
PHST- 2018/09/06 06:00 [entrez]
PHST- 2018/09/06 06:00 [pubmed]
PHST- 2019/11/26 06:00 [medline]
PHST- 2018/10/08 00:00 [pmc-release]
AID - S2211-1247(18)31263-4 [pii]
AID - 10.1016/j.celrep.2018.08.009 [doi]
PST - ppublish
SO  - Cell Rep. 2018 Sep 4;24(10):2723-2732.e4. doi: 10.1016/j.celrep.2018.08.009.