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TitleStructure basis of neutralization by a novel site II/IV antibody against respiratory syncytial virus fusion protein.
Journal, issue, pagesPLoS One, Vol. 14, Issue 2, Page e0210749, Year 2019
Publish dateFeb 7, 2019
AuthorsQingqing Xie / Zhao Wang / Fengyun Ni / Xiaorui Chen / Jianpeng Ma / Nita Patel / Hanxin Lu / Ye Liu / Jing-Hui Tian / David Flyer / Michael J Massare / Larry Ellingsworth / Gregory Glenn / Gale Smith / Qinghua Wang /
PubMed AbstractGlobally, human respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in newborns, young children, and the elderly for which there is no vaccine. The RSV fusion ...Globally, human respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in newborns, young children, and the elderly for which there is no vaccine. The RSV fusion (F) glycoprotein is a major target for vaccine development. Here, we describe a novel monoclonal antibody (designated as R4.C6) that recognizes both pre-fusion and post-fusion RSV F, and binds with nanomole affinity to a unique neutralizing site comprised of antigenic sites II and IV on the globular head. A 3.9 Å-resolution structure of RSV F-R4.C6 Fab complex was obtained by single particle cryo-electron microscopy and 3D reconstruction. The structure unraveled detailed interactions of R4.C6 with antigenic site II on one protomer and site IV on a neighboring protomer of post-fusion RSV F protein. These findings significantly further our understanding of the antigenic complexity of the F protein and provide new insights into RSV vaccine design.
External linksPLoS One / PubMed:30730999 / PubMed Central
MethodsEM (single particle)
Resolution3.9 Å
Structure data

7774

6cxc

EMDB-7774, PDB-6cxc:
3.9A Cryo-EM structure of murine antibody bound at a novel epitope of respiratory syncytial virus fusion protein
Method: EM (single particle) / Resolution: 3.9 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • mus musculus (house mouse)
  • Human respiratory syncytial virus A2
  • human immunodeficiency virus 1
  • human respiratory syncytial virus a (strain a2)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / respiratory syncytial virus fusion protein / murine antibody / novel epitope / complex / VIRAL PROTEIN-IMMUNE SYSTEM complex

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