Heparan sulphate binding controls in vivo half-life of the HpARI protein family

• DOI: 10.7554/elife.99000.1
• Publication Date: 2024-08-27T12:26:39Z
• Authors: Florent Colomb; Abhishek Jamwal; Adefunke Ogunkanbi; Tania Frangova; Alice R Savage; Sarah Kelly; Gavin J Wright; Matthew K Higgins; Henry J McSorley
• Keywords: Heligmosomoides polygyrus

The parasitic nematode Heligmosomoides polygyrus bakeri secretes the HpARI family, which bind to IL-33, either suppressing (HpARI1 and HpARI2) or enhancing (HpARI3) responses cytokine. We previously showed that HpARI2 also bound DNA via its first Complement Control Protein (CCP1) domain. Here, we find HpARI1 can DNA, while HpARI3 cannot. Through production of HpARI2/HpARI3 CCP1 domain-swapped chimeras, DNA-binding ability be transferred, correlates with in vivo half-life administered proteins. found (but not HpARI3) binds extracellular matrix component heparan sulphate (HS), structural modelling a basic charged patch domain could facilitate these interactions. Finally, mutant was produced lacked HS binding, shown have short vivo. Therefore, propose during infection suppressive proteins long-lasting effects, may retained at sites and/or Conversely, shorter effects where deposited, but diffuse distal sites.