
기생충 H. polygyrus bakeri에서 분비되는 HpARI 단백질 군은 세포외 기질 결합을 통해 체내 반감기를 조절하여 숙주 내 IL-33 반응을 차별적으로 조절합니다.


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

### Competing Interest Statement

The authors have declared no competing interest.

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

헤파란-황산염-결합-hpari-단백질-군의-체내-반감기에-미치는-영향


헤파란 황산염 결합: HpARI 단백질 군의 체내 반감기에 미치는 영향
