Nature Communications (Nov 2021)

Extended antibody-framework-to-antigen distance observed exclusively with broad HIV-1-neutralizing antibodies recognizing glycan-dense surfaces

  • Myungjin Lee,
  • Anita Changela,
  • Jason Gorman,
  • Reda Rawi,
  • Tatsiana Bylund,
  • Cara W. Chao,
  • Bob C. Lin,
  • Mark K. Louder,
  • Adam S. Olia,
  • Baoshan Zhang,
  • Nicole A. Doria-Rose,
  • Susan Zolla-Pazner,
  • Lawrence Shapiro,
  • Gwo-Yu Chuang,
  • Peter D. Kwong

DOI
https://doi.org/10.1038/s41467-021-26579-z
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 10

Abstract

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Here, the authors analyse the distance between the body of an antibody and a protein antigen denoted as the Antibody-Framework-to-Antigen Distance (AFAD) for about 2000 non-redundant antibody-protein antigen complexes in the Protein Data Bank. They observe that antibodies with exceptionally long AFADs were all broad HIV-1-neutralizing antibodies that targeted densely glycosylated regions on the HIV-1-envelope trimer. The connection between long AFAD and dense glycan was further validated by the cryo-EM structure of antibody 2909 recognizing a glycan hole and by glycan shielding analyses based on molecular dynamics simulations.