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Updated: May 29, 2026

Identifying the Binding Proteins of Small Ligands with the Differential Radial Capillary Action of Ligand Assay (DRaCALA)
Published on: March 19, 2021
Lipocalin Q83 reveals a dual ligand binding mode with potential implications for the functions of siderocalins
Nicolas Coudevylle1, Matthias Hoetzinger, Leonhard Geist
1Department of Structural and Computational Biology, Max F Perutz Laboratories, University of Vienna, Campus Vienna Biocenter 5/1, 1030 Vienna, Austria. nicolas.coudevylle@univie.ac.at
Abstract:
Siderocalins are particular lipocalins that participate in the innate immune response by interfering with bacterial siderophore-mediated iron uptake. Additionally, siderocalins are involved in several physiological and pathological processes such as inflammation, iron delivery, tissue differentiation, and cancer progression. Here we show that siderocalin Q83 displays an unexpected dual ligand binding mode as it can bind enterobactin and unsaturated fatty acids simultaneously. The solution structure of the siderocalin Q83 in complex with arachidonic acid and enterobactin reveals molecular details of this novel dual binding mode and the determinants of fatty acid binding specificity. Our results suggest that Q83 is a metabolic hub linking iron and fatty acid pathways. This unexpected coupling might contribute to the pleiotropic functions of siderocalins.
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