High-resolution asymmetric structure of a Fab-virus complex reveals overlap with the receptor binding site.

Autor:	Goetschius DJ; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802., Hartmann SR; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802., Organtini LJ; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802., Callaway H; Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853., Huang K; Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853., Bator CM; Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802., Ashley RE; Department of Medicine, Penn State University College of Medicine, The Pennsylvania State University, Hershey, PA 17033., Makhov AM; Department of Structural Biology, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260., Conway JF; Department of Structural Biology, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260., Parrish CR; Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853., Hafenstein SL; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802; shafenstein@psu.edu.; Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802.; Department of Medicine, Penn State University College of Medicine, The Pennsylvania State University, Hershey, PA 17033.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Jun 08; Vol. 118 (23).
DOI:	10.1073/pnas.2025452118
Abstrakt:	Canine parvovirus is an important pathogen causing severe diseases in dogs, including acute hemorrhagic enteritis, myocarditis, and cerebellar disease. Overlap on the surface of parvovirus capsids between the antigenic epitope and the receptor binding site has contributed to cross-species transmission, giving rise to closely related variants. It has been shown that Mab 14 strongly binds and neutralizes canine but not feline parvovirus, suggesting this antigenic site also controls species-specific receptor binding. To visualize the conformational epitope at high resolution, we solved the cryogenic electron microscopy (cryo-EM) structure of the Fab-virus complex. We also created custom software, Icosahedral Subparticle Extraction and Correlated Classification, to solve a Fab-virus complex with only a few Fab bound per capsid and visualize local structures of the Fab-bound and -unbound antigenic sites extracted from the same complex map. Our results identified the antigenic epitope that had significant overlap with the receptor binding site, and the structures revealed that binding of Fab induced conformational changes to the virus. We were also able to assign the order and position of attached Fabs to allow assessment of complementarity between the Fabs bound to different positions. This approach therefore provides a method for using cryo-EM to investigate complementarity of antibody binding. Competing Interests: The authors declare no competing interest. (Copyright © 2021 the Author(s). Published by PNAS.)
Databáze:	MEDLINE
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