5O9L

Crystal structure of human Histamine-Releasing Factor (HRF/TCTP)

Summary for 5O9L

• Entry DOI: 10.2210/pdb5o9l/pdb
• Descriptor: Translationally-controlled tumor protein (2 entities in total)
• Functional Keywords: immunoglobulin e, allergy, histamine releasing factor, tctp, hrf, p23, p21, fortilin, immune system
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : P13693
• Total number of polymer chains: 2
• Total formula weight: 41381.00

Authors

Dore, K.A.,Kashiwakura, J.,McDonnell, J.M.,Gould, H.J.,Kawakami, T.,Sutton, B.J.,Davies, A.M. (deposition date: 2017-06-19, release date: 2017-12-20, Last modification date: 2024-01-17)

Primary citation

Dore, K.A.,Kashiwakura, J.I.,McDonnell, J.M.,Gould, H.J.,Kawakami, T.,Sutton, B.J.,Davies, A.M.
Crystal structures of murine and human Histamine-Releasing Factor (HRF/TCTP) and a model for HRF dimerisation in mast cell activation.
Mol. Immunol., 93:216-222, 2017

PubMed Abstract: 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 4.0Å resolution, revealing a conserved fold. We also solved the structure of human HRF (hHRF) in two new crystal forms, one at the highest resolution (1.4Å) 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.

PubMed: 29216544
DOI: 10.1016/j.molimm.2017.11.022

Experimental method

X-RAY DIFFRACTION (1.75 Å)