Resource availability
Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact, Erica Ollmann Saphire ([email protected]).
Data availability
Structure factors and associated model coordinates have been deposited in the Protein Data Bank (PDB; http://www.rcsb.org) under PDB accession numbers 7RPU (3A6 Fab-stalk–MPER) and 7RPT (3A6 Fab structure).
Code availability
Not applicable.
Acknowledgements
We are grateful to Dustin Morado, Kun Qu, and Joaquin Oton (Medical Research Council Laboratory of Molecular Biology) for support in collecting and/or processing cryogenic electron tomography data and to Stanford Synchrotron Light Source (SSRL) and Advanced Photon Source (APS) for assistance in collection of X-ray data. We thank Anya Crane (National Institutes of Health [NIH], National Institute of Allergy and Infectious Diseases [NIAID], Integrated Research Facility at Fort Detrick, Frederick, MD, USA [IRF-Frederick]) for critically editing the manuscript and Jiro Wada (NIH NIAID IRF-Frederick) for creating figures. We gratefully acknowledge Peter B. Jahrling and Lisa E. Hensley (NIH NIAID IRF-Frederick) for supporting the studies involving animals.
The work for this study was supported by NIH NIAID U19 AI142790 (E.O.S. and C.W.D.), DARPA contract W31P4Q-14-1-0010 (C.W.D. and R.A.), NIH NIAID contract HHSN272201400058C to B.J.D., and UK Medical Research Council (MC_UP_1201/16), the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (ERC-CoG-648432 MEMBRANEFUSION), and the Max Planck Society (J.B.). This research was further supported through the NIH/NIAID prime contract with Battelle Memorial Institute (Contract No. HHSN272200700016I) and subsequently with Laulima Government Solutions (Contract No. HHSN272201800013C). G.W. and M.R.H. performed this work as employee under these contracts. J.H.K. performed this work partly as an employee under the Battelle Memorial Institute contract and partly as an employee of Tunnell Government Services, formerly a subcontractor of Battelle Memorial Institute and now of Laulima Government Solutions. This work has been further funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261201500003I, Task Order No. HHSN26100043 and Contract No. 75N91019D00024, Task Order No. 75N91019F00130 (I.C.). S.M. was funded by an Imaging Scientist grant (2019‐198153) from the Chan Zuckerberg Initiative.
Use of the SSRL SLAC National Accelerator Laboratory is supported by the US Department of Energy (DOE) Office of Science Basic Energy Sciences (BES) program under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Biological and Environmental Research (BER) program and by the NIH National Institute of General Medical Sciences (NIGMS; P41GM103393). This research also used resources of the Advanced Photon Source (APS), a DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory (ANL) under Contract No. DE-AC02-06CH11357. The General Medical Sciences and Cancer Institute Structural Biology Facility at the Advanced Photon Source (GM/CA) project has been funded in whole or in part with Federal funds from the National Cancer Institute (ACB-12002) and the NIGMS (AGM-12006). The Eiger 16M detector at the ANL X-ray Science Division (XSD) was funded by NIH grant S10 OD012289.
Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. The funding sources had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
The views and conclusions contained in this document are those of the authors and should not be interpreted as necessarily representing the official policies, either expressed or implied, of the U.S. Department of Health and Human Services or of the institutions and companies affiliated with the authors, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
Contributions
Conceptualization, Z.L.S., J.A.G.B., G.W., C.W.D., R.A., and E.O.S.
Methodology, Z.L.S., Z.K., E.D., B.D., and E.O.S.
Investigation, Z.L.S., Z.K., P.J.H., E.D., C.C., C.H., S.M., M.J.N., and X.X.
Formal analysis, Z.L.S., X.Y., Z.K., J.A.G.B., G.W., E.O.S.,
Writing—Original Draft, Z.L.S. and E.O.S.
Writing—Review & Editing, S.L.S., Z.L.S., X.Y., I.C., J.H.K., J.A.G.B., G.W., R.A., and E.O.S.
Visualization, Z.L.S, X.Y., S.M.
Supervision, B.D., Y.K., J.A.G.B., and E.O.S.
Resources, B.D., P.B.J., I.C., and J.H.K.
Funding Acquisition, J.A.G.B., C.W.D., R.A., and E.O.S.
Ethics declarations
Study compliance
Animal exposure and treatment experiments using infectious EBOV were performed in registered and accredited biosafety level 4 (BSL-4) laboratories with appropriate approvals.
Competing interests
A.G., E.D., and B.J.D. are employees of Integral Molecular, and B.J.D.is a shareholder in that company.