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Publication Abstract from PubMed

In allergic disease, mast cell activation is conventionally triggered by allergen-mediated cross-linking of receptor-bound IgE on the cell surface. In addition to its diverse range of intracellular roles in apoptosis, cell proliferation and cancer, Histamine-Releasing Factor (HRF) also activates mast cells and basophils. A subset of IgE antibodies bind HRF through their Fab regions, and two IgE binding sites on HRF have been mapped. HRF can form dimers, and a disulphide-linked dimer is critical for activity. The current model for the activity of HRF in mast cell activation involves cross-linking of receptor-bound IgE by dimeric HRF, mediated by HRF/Fab interactions. HRF crystal and solution structures have provided little insight into either the formation of disulphide-linked HRF dimers or the ability of HRF to activate mast cells. We report the first crystal structure of murine HRF (mHRF) to 4.0A resolution, revealing a conserved fold. We also solved the structure of human HRF (hHRF) in two new crystal forms, one at the highest resolution (1.4A) yet reported. The high resolution hHRF structure reveals a disulphide-linked dimer, in which the two molecules are closely associated, and provides a model for the role of both human and murine HRF in mast cell activation.

Crystal structures of murine and human Histamine-Releasing Factor (HRF/TCTP) and a model for HRF dimerisation in mast cell activation.,Dore KA, Kashiwakura JI, McDonnell JM, Gould HJ, Kawakami T, Sutton BJ, Davies AM Mol Immunol. 2018 Jan;93:216-222. doi: 10.1016/j.molimm.2017.11.022. Epub 2017, Dec 5. PMID:29216544^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.