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Yorodumi- PDB-7nks: Structure of the Hantaan virus Gn glycoprotein ectodomain in comp... -
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-Basic information
Entry | Database: PDB / ID: 7nks | ||||||||||||||||||||||||||||||||||||
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Title | Structure of the Hantaan virus Gn glycoprotein ectodomain in complex with Fab HTN-Gn1 | ||||||||||||||||||||||||||||||||||||
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Keywords | VIRAL PROTEIN / Hantaan virus glycoprotein / Gn glycoprotein / Fab / neutralizing antibody / viral glycoprotein in complex with antibody | ||||||||||||||||||||||||||||||||||||
Function / homology | Function and homology information symbiont-mediated suppression of host TRAF-mediated signal transduction / host cell Golgi membrane / host cell mitochondrion / host cell surface / host cell endoplasmic reticulum membrane / virus-mediated perturbation of host defense response / virion membrane / signal transduction / membrane / metal ion binding Similarity search - Function | ||||||||||||||||||||||||||||||||||||
Biological species | Hantaan orthohantavirus Oryctolagus cuniculus (rabbit) | ||||||||||||||||||||||||||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.5 Å | ||||||||||||||||||||||||||||||||||||
Authors | Rissanen, I. / Bowden, T.A. / Huiskonen, J.T. / Stass, R. | ||||||||||||||||||||||||||||||||||||
Funding support | United Kingdom, Finland, United States, 11items
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Citation | Journal: mBio / Year: 2021 Title: Structural Basis for a Neutralizing Antibody Response Elicited by a Recombinant Hantaan Virus Gn Immunogen. Authors: Ilona Rissanen / Stefanie A Krumm / Robert Stass / Annalis Whitaker / James E Voss / Emily A Bruce / Sylvia Rothenberger / Stefan Kunz / Dennis R Burton / Juha T Huiskonen / Jason W Botten / ...Authors: Ilona Rissanen / Stefanie A Krumm / Robert Stass / Annalis Whitaker / James E Voss / Emily A Bruce / Sylvia Rothenberger / Stefan Kunz / Dennis R Burton / Juha T Huiskonen / Jason W Botten / Thomas A Bowden / Katie J Doores / Abstract: Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two ...Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two glycoproteins, Gn and Gc, which are responsible for negotiating host cell entry and constitute key therapeutic targets. Here, we demonstrate that recombinantly derived Gn from Hantaan virus (HTNV) elicits a neutralizing antibody response (serum dilution that inhibits 50% infection [ID], 1:200 to 1:850) in an animal model. Using antigen-specific B cell sorting, we isolated monoclonal antibodies (mAbs) exhibiting neutralizing and non-neutralizing activity, termed mAb HTN-Gn1 and mAb nnHTN-Gn2, respectively. Crystallographic analysis reveals that these mAbs target spatially distinct epitopes at disparate sites of the N-terminal region of the HTNV Gn ectodomain. Epitope mapping onto a model of the higher order (Gn-Gc) spike supports the immune accessibility of the mAb HTN-Gn1 epitope, a hypothesis confirmed by electron cryo-tomography of the antibody with virus-like particles. These data define natively exposed regions of the hantaviral Gn that can be targeted in immunogen design. The spillover of pathogenic hantaviruses from rodent reservoirs into the human population poses a continued threat to human health. Here, we show that a recombinant form of the Hantaan virus (HTNV) surface-displayed glycoprotein, Gn, elicits a neutralizing antibody response in rabbits. We isolated a neutralizing (HTN-Gn1) and a non-neutralizing (nnHTN-Gn2) monoclonal antibody and provide the first molecular-level insights into how the Gn glycoprotein may be targeted by the antibody-mediated immune response. These findings may guide rational vaccine design approaches focused on targeting the hantavirus glycoprotein envelope. | ||||||||||||||||||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
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PDBx/mmCIF format | 7nks.cif.gz | 622.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7nks.ent.gz | 515.9 KB | Display | PDB format |
PDBx/mmJSON format | 7nks.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7nks_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7nks_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 7nks_validation.xml.gz | 53.6 KB | Display | |
Data in CIF | 7nks_validation.cif.gz | 72.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nk/7nks ftp://data.pdbj.org/pub/pdb/validation_reports/nk/7nks | HTTPS FTP |
-Related structure data
Related structure data | 7nrhC 7o9sC 5m63S 5opgS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
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-Assembly
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Noncrystallographic symmetry (NCS) | NCS domain:
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