Haptoglobin (HP) is a protein mostly made in the liver that binds to free hemoglobin (the part of red blood cells that carries oxygen). When HP binds to hemoglobin, it helps remove this potentially harmful substance from the blood, protecting the kidneys during the breakdown of red blood cells1.
There are different forms of HP in humans, leading to three main types2, which are linked to various diseases, including type 1 diabetes3 and inflammatory bowel disease (IBD)4. Recently, researchers discovered that the precursor to haptoglobin, called pre-haptoglobin-2 (or zonulin), is important for celiac disease5 – an autoimmune disease where ingestion of gluten causes an abnormal immune response. It is estimated to affect about 1% of the world population and there is currently no cure, with the only treatment being a life-long gluten-free diet.
This HALRIC pilot project is a new collaboration between researchers in Hamburg and Aarhus and it offers an opportunity for the structural characterization of targets using an integrative structural biology approach. The goal of the project is to study the structure of zonulin and understand its roles better, including:
1) Using cryogenic electron microscopy (cryo EM) to structurally characterise the oligomeric assemblies of zonulin.
2) Validate the role of zonulin in celiac disease by performing an ELISA assay on serum.
3) Continue ongoing efforts to crystallise and determine the structure of full-length zonulin.
The University Medical Center Hamburg-Eppendorf (UKE) also joins as co-proposer to assess the clinical relevance of zonulin and its potential role as biomarker in IBD.
For further information about this HALRIC pilot project, please contact:
jialing.song@desy.de
References:
1. Biochem Mosc Suppl B Biomed Chem., 15(3): 184–198 (2021)
2. Gen. and Mol. Biol., 31, 3,602-620 (2008)
3. J Autoimmun., 122:102674 (2021)
4. J Clin Med 2021; 10: 3905
5. PNAS, 106(39):16799-804 (2009)
