Format

Send to

Choose Destination
Mol Immunol. 2018 Jan;93:216-222. doi: 10.1016/j.molimm.2017.11.022. Epub 2017 Dec 5.

Crystal structures of murine and human Histamine-Releasing Factor (HRF/TCTP) and a model for HRF dimerisation in mast cell activation.

Author information

1
King's College London, Randall Centre for Cell and Molecular Biophysics, New Hunt's House, London, SE1 1UL, United Kingdom; Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom.
2
Laboratory for Allergic Disease, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
3
Laboratory for Allergic Disease, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan; Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA; Department of Dermatology, University of California San Diego, School of Medicine, La Jolla, CA, 92093, USA.
4
King's College London, Randall Centre for Cell and Molecular Biophysics, New Hunt's House, London, SE1 1UL, United Kingdom; Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom. Electronic address: brian.sutton@kcl.ac.uk.
5
King's College London, Randall Centre for Cell and Molecular Biophysics, New Hunt's House, London, SE1 1UL, United Kingdom; Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom. Electronic address: anna.davies@kcl.ac.uk.

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.

KEYWORDS:

Allergy; Histamine-Releasing Factor; Immunoglobulin E

PMID:
29216544
PMCID:
PMC5966295
DOI:
10.1016/j.molimm.2017.11.022
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center