3jcx Citations

Near-Atomic Resolution Structure of a Highly Neutralizing Fab Bound to Canine Parvovirus.

Abstract

Canine parvovirus (CPV) is a highly contagious pathogen that causes severe disease in dogs and wildlife. Previously, a panel of neutralizing monoclonal antibodies (MAb) raised against CPV was characterized. An antibody fragment (Fab) of MAb E was found to neutralize the virus at low molar ratios. Using recent advances in cryo-electron microscopy (cryo-EM), we determined the structure of CPV in complex with Fab E to 4.1 Å resolution, which allowed de novo building of the Fab structure. The footprint identified was significantly different from the footprint obtained previously from models fitted into lower-resolution maps. Using single-chain variable fragments, we tested antibody residues that control capsid binding. The near-atomic structure also revealed that Fab binding had caused capsid destabilization in regions containing key residues conferring receptor binding and tropism, which suggests a mechanism for efficient virus neutralization by antibody. Furthermore, a general technical approach to solving the structures of small molecules is demonstrated, as binding the Fab to the capsid allowed us to determine the 50-kDa Fab structure by cryo-EM.

Reviews - 3jcx mentioned but not cited (1)

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Reviews citing this publication (4)

  1. Twenty-Five Years of Structural Parvovirology. Mietzsch M, Pénzes JJ, Agbandje-McKenna M. Viruses 11 E362 (2019)
  2. Applications of Charge Detection Mass Spectrometry in Molecular Biology and Biotechnology. Jarrold MF. Chem Rev 122 7415-7441 (2022)
  3. Small but mighty: old and new parvoviruses of veterinary significance. Jager MC, Tomlinson JE, Lopez-Astacio RA, Parrish CR, Van de Walle GR. Virol J 18 210 (2021)
  4. Parvovirus Capsid-Antibody Complex Structures Reveal Conservation of Antigenic Epitopes Across the Family. Emmanuel SN, Mietzsch M, Tseng YS, Smith JK, Agbandje-McKenna M. Viral Immunol 34 3-17 (2021)

Articles citing this publication (15)