7B26

CirpA1 in complex with pseudo-monomeric Properdin lacking TSR2-3

Summary for 7B26

• Entry DOI: 10.2210/pdb7b26/pdb
• Related: 7B28 7B29 7B2A 7B2D
• Descriptor: Properdin, CirpA1, beta-D-glucopyranose-(1-3)-alpha-L-fucopyranose, ... (5 entities in total)
• Functional Keywords: inhibitor, complement, tick, complex, immunosuppressant
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 64349.33

Authors

Lea, S.M.,Johnson, S.,Braunger, K. (deposition date: 2020-11-26, release date: 2021-12-08, Last modification date: 2024-11-20)

Primary citation

Braunger, K.,Ahn, J.,Jore, M.M.,Johnson, S.,Tang, T.T.L.,Pedersen, D.V.,Andersen, G.R.,Lea, S.M.
Structure and function of a family of tick-derived complement inhibitors targeting properdin.
Nat Commun, 13:317-317, 2022

PubMed 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.

PubMed: 35031611
DOI: 10.1038/s41467-021-27920-2

Experimental method

X-RAY DIFFRACTION (3.4 Å)