Structure and function of a family of tick-derived complement inhibitors targeting properdin

Katharina Braunger, Jiyoon Ahn, Matthijs M. Jore, Steven Johnson (), Terence T. L. Tang, Dennis V. Pedersen, Gregers R. Andersen and Susan M. Lea ()
Additional contact information
Katharina Braunger: University of Oxford
Jiyoon Ahn: University of Oxford
Matthijs M. Jore: University of Oxford
Steven Johnson: University of Oxford
Terence T. L. Tang: University of Oxford
Dennis V. Pedersen: Aarhus University
Gregers R. Andersen: Aarhus University
Susan M. Lea: University of Oxford

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Activation of the serum-resident complement system begins a cascade that leads to activation of membrane-resident complement receptors on immune cells, thus coordinating serum and cellular immune responses. Whilst many molecules act to control inappropriate activation, Properdin is the only known positive regulator of the human complement system. By stabilising the alternative pathway C3 convertase it promotes complement self-amplification and persistent activation boosting the magnitude of the serum complement response by all triggers. In this work, we identify a family of tick-derived alternative pathway complement inhibitors, hereafter termed CirpA. Functional and structural characterisation reveals that members of the CirpA family directly bind to properdin, inhibiting its ability to promote complement activation, and leading to potent inhibition of the complement response in a species specific manner. We provide a full functional and structural characterisation of a properdin inhibitor, opening avenues for future therapeutic approaches.

Date: 2022
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-27920-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27920-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-27920-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().