NMR residual dipolar couplings investigation in the topology of house dust mite Group V allergens

J Struct Biol. 2024 Dec;216(4):108138. doi: 10.1016/j.jsb.2024.108138. Epub 2024 Oct 22.

Abstract

Blo t 5 is an important major allergen protein from Blomia tropicalis mites, which are prevalent in tropical and subtropical regions, including Taiwan. It is a coiled-coil triple helical bundle, but there currently is ambiguity around its structural fold and packing of the three helices. We have relied on NMR residual dipolar coupling data collected from four different alignment media to confirm that Blo t 5 has left-handed helical topology and further used that data to refine its solution structure. Earlier we had described conformational epitope for a detection monoclonal antibody by exclusive use of TROSY NMR experiments that studied Blo t 5 binding with the antibody FAB' fragment. Here, we confirm those findings with an extensive mutagenesis and biophysical study to validate the NMR epitope mapping approach proposed by us.

Keywords: House dust mites; Hypoallergenic protein; Immunotherapy; Major allergen; NMR; Residual dipolar coupling; Solution structure; Structure-based design.

MeSH terms

  • Allergens* / chemistry
  • Allergens* / immunology
  • Amino Acid Sequence
  • Animals
  • Epitope Mapping / methods
  • Epitopes / chemistry
  • Epitopes / immunology
  • Magnetic Resonance Spectroscopy / methods
  • Nuclear Magnetic Resonance, Biomolecular / methods
  • Protein Conformation
  • Pyroglyphidae* / chemistry
  • Pyroglyphidae* / immunology

Substances

  • Allergens
  • Epitopes