6RQJ

Structure of human complement C5 complexed with tick inhibitors OmCI, RaCI1 and CirpT1

Summary for 6RQJ

• Entry DOI: 10.2210/pdb6rqj/pdb
• Related: 6rpt
• EMDB information: 4983
• Descriptor: Complement C5, Complement inhibitor, Rhipicephalus appendiculatus RaCI1, ... (6 entities in total)
• Functional Keywords: complement, inhibitor, innate immunity, inflammation, c5, terminal pathway inhibitor, immunosuppressant
• Biological source: Rhipicephalus pulchellus; More
• Total number of polymer chains: 5
• Total formula weight: 225798.83

Authors

Reichhardt, M.P.,Johnson, S.,Lea, S.M. (deposition date: 2019-05-15, release date: 2020-01-08, Last modification date: 2024-11-06)

Primary citation

Reichhardt, M.P.,Johnson, S.,Tang, T.,Morgan, T.,Tebeka, N.,Popitsch, N.,Deme, J.C.,Jore, M.M.,Lea, S.M.
An inhibitor of complement C5 provides structural insights into activation.
Proc.Natl.Acad.Sci.USA, 117:362-370, 2020

PubMed Abstract: The complement system is a crucial part of innate immune defenses against invading pathogens. The blood-meal of the tick lasts for days, and the tick must therefore rely on inhibitors to counter complement activation. We have identified a class of inhibitors from tick saliva, the CirpT family, and generated detailed structural data revealing their mechanism of action. We show direct binding of a CirpT to complement C5 and have determined the structure of the C5-CirpT complex by cryoelectron microscopy. This reveals an interaction with the peripheral macro globulin domain 4 (C5_MG4) of C5. To achieve higher resolution detail, the structure of the C5_MG4-CirpT complex was solved by X-ray crystallography (at 2.7 Å). We thus present the fold of the CirpT protein family, and provide detailed mechanistic insights into its inhibitory function. Analysis of the binding interface reveals a mechanism of C5 inhibition, and provides information to expand our biological understanding of the activation of C5, and thus the terminal complement pathway.

PubMed: 31871188
DOI: 10.1073/pnas.1909973116

Experimental method

ELECTRON MICROSCOPY (3.5 Å)