Featured
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Article
| Open Access
Structural basis for membrane attack complex inhibition by CD59
CD59 protects human cells from damage by the MAC immune pore. The authors show how CD59 inhibits MAC, by deflecting pore-forming β-hairpins of complement proteins. As well as how the membrane environment influences the role of CD59 in complement regulation and in host-pathogen interactions.
- Emma C. Couves
- , Scott Gardner
- & Doryen Bubeck
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Article
| Open Access
The complement C3-complement factor D-C3a receptor signalling axis regulates cardiac remodelling in right ventricular failure
Right ventricular (RV) failure is clinically crucial, but there is no specific therapy. Here, the authors show that the complement alternative pathway is activated in RV failure and that blockade of the pathway ameliorates RV failure in mice.
- Shogo Ito
- , Hisayuki Hashimoto
- & Shinsuke Yuasa
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Article
| Open Access
Structure and function of a family of tick-derived complement inhibitors targeting properdin
Properdin is the only known positive regulator of the human complement system, stabilising the convertase C3 in the alternative pathway of complement activation. Here, the authors report the identification and characterisation of a species-specific properdin inhibitor CirpA, derived from tick saliva.
- Katharina Braunger
- , Jiyoon Ahn
- & Susan M. Lea
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Article
| Open Access
Targets of complement-fixing antibodies in protective immunity against malaria in children
Antibodies against Plasmodium falciparum merozoites that fix complement can inhibit blood-stage replication. Here, Reiling et al. show that complement-fixing antibodies strongly correlate with protective immunity in children, identify the merozoite targets, and predict antigen combinations that should result in strong protection.
- Linda Reiling
- , Michelle J. Boyle
- & James G. Beeson
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Article
| Open Access
MafB is a critical regulator of complement component C1q
Complement component C1q activates efferocytosis, suppresses inflammatory responses, and is thereby thought to limit autoimmune disease. Here, the authors show that macrophage transcription factor MafB regulates total serum levels of C1q, which contributes to preventing autoimmune disease in mice.
- Mai Thi Nhu Tran
- , Michito Hamada
- & Satoru Takahashi
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Article
| Open Access
Exploiting a novel conformational switch to control innate immunity mediated by complement protein C3a
Complement C3a is an important protein in innate and adaptive immunity, but its roles in vivo are unclear. Here the authors develop novel chemical agonists and antagonists for the C3a receptor, and show that they modulate mast cell degranulation and inflammation in a rat paw edema model
- Rink-Jan Lohman
- , Johan K. Hamidon
- & David P. Fairlie
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Article
| Open Access
Structure of the poly-C9 component of the complement membrane attack complex
The membrane attack complex is a heteromeric assembly of complement proteins where multiple copies of C9 are recruited by the C5b678 complex to form lytic pores in pathogen membranes. Here the authors present the structure of a soluble pore-like form of the C9 component that reveals details of the oligomerization interfaces.
- Natalya V. Dudkina
- , Bradley A. Spicer
- & Michelle A. Dunstone
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Article
| Open Access
Complement anaphylatoxin C3a is a potent inducer of embryonic chick retina regeneration
Components of the complement system have been shown to promote liver regeneration. Haynes et al. demonstrate that the complement fragment C3a can induce regeneration of the embryonic chick retina from stem and progenitor cells of the ciliary margin via activation of STAT3 and other downstream signalling pathways.
- Tracy Haynes
- , Agustin Luz-Madrigal
- & Katia Del Rio-Tsonis
Complement is activated by elevated IgG3 hexameric platforms and deposits C4b onto distinct antibody domains