Antigen-Induced Allosteric Changes in a Human IgG1 Fc Increase Low-Affinity Fcγ Receptor Binding

Chiara Orlandi, Daniel Deredge, Krishanu Ray, Neelakshi Gohain, William Tolbert, Anthony L. DeVico, Patrick Wintrode, Marzena Pazgier, George K. Lewis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Orlandi et al. show that antigen binding to Fab increases binding of IgG1 Fc to low-affinity FcγR by conformational allostery. Leucine to alanine mutations at positions 234 and 235 in the lower hinge of IgG1 globally alter Fc structure and biological activity by configurational allostery.

Original languageEnglish
Pages (from-to)516-527.e5
JournalStructure
Volume28
Issue number5
DOIs
StatePublished - 5 May 2020
Externally publishedYes

Keywords

  • Fc receptor binding
  • Fc-effector function
  • HDX-MS
  • IgG1 LALA variants
  • RFADCC Assay
  • antigen binding
  • configurational allostery
  • conformational allostery
  • immunoglobulin

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