8PIH

Structure of Api m1 in complex with two nanobodies

Summary for 8PIH

• Entry DOI: 10.2210/pdb8pih/pdb
• Descriptor: Phospholipase A2, nanobody AM1-4, nanobdoy AM1-1, ... (5 entities in total)
• Functional Keywords: allergen, antibody, nanobody
• Biological source: Lama glama; More
• Total number of polymer chains: 3
• Total formula weight: 41692.87

Authors

Aagaard, J.B.,Gandini, R.,Spillner, E.,Miehe, M.,Andersen, G.R. (deposition date: 2023-06-21, release date: 2024-05-08, Last modification date: 2026-07-01)

Primary citation

Aagaard, J.B.,Gandini, R.,Ballegaard, A.R.,Jensen, B.K.,Dorn, B.,Larsen, A.V.B.,Lenstrup, A.,Sonderholm, M.,Miehe, M.,Pfutzner, W.,Jakob, T.,Andersen, G.R.,Mobs, C.,Spillner, E.
Nanobody-based IgG simultaneously inhibit the allergenic and enzymatic activity of the dominant honeybee venom allergen.
Nat Commun, 17:1814-1814, 2026

PubMed Abstract: Insect venoms can cause severe allergic reactions, including anaphylaxis, in sensitized individuals. In this study, we aim at preventing anaphylaxis mediated by the most abundant and dominant honeybee venom allergen phospholipase A2 (Api m 1) by blocking its interaction with allergic patient IgE. Therefore, we characterize selected Api m 1-specific nanobodies and identify two high-affinity binders with non-overlapping epitopes. Crystal structures of Api m 1/nanobody complexes reveal diametrically opposed epitopes, one of which involves the active site of Api m 1. Based on this background, we develop mono- and bispecific nanobody-human IgG Fc, which exhibits pronounced blocking of IgE binding and effector cell activation in blood samples from honeybee venom allergic patients and reduces systemic reactions in a mouse model of allergen-induced anaphylaxis. This work provides a rationale for using nanobody-based inhibitors to prevent Api m 1-mediated anaphylaxis in honeybee venom allergy.

PubMed: 41702899
DOI: 10.1038/s41467-026-69572-0

Experimental method

X-RAY DIFFRACTION (1.76 Å)