ArticleThe Journal of biological chemistry2012
Crystal structure of C5b-6 suggests structural basis for priming assembly of the membrane attack complex.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 69 citations in OpenAlex.
- Article
- Expanding the landscape of BREX diversity: uncovering multi-layered functional frameworks and identification of novel BREX-related defense systems.Nucleic acids research · 2026Article
- Action of the Terminal Complement Pathway on Cell Membranes.The Journal of membrane biology · 2025Review
- Methods for detecting, building, and improving tryptophan mannosylation in glycoprotein structures.Protein science : a publication of the Protein Society · 2025Article
- The Complement System.Advances in experimental medicine and biology · 2025Review
- Development, Characterization, and in vivo Validation of a Humanized C6 Monoclonal Antibody that Inhibits the Membrane Attack Complex.Journal of innate immunity · 2023Article
- Cryo-EM structures of human A2ML1 elucidate the protease-inhibitory mechanism of the A2M family.Nature communications · 2022Article
- A Conformational Change of Complement C5 Is Required for Thrombin-Mediated Cleavage, Revealed by a Novel Ex Vivo Human Whole Blood Model Preserving Full Thrombin Activity.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- ProteinMolecules (Basel, Switzerland) · 2021Review
- More than a Pore: Nonlytic Antimicrobial Functions of Complement and Bacterial Strategies for Evasion.Microbiology and molecular biology reviews : MMBR · 2021Review
- Article
- Immune Evasion Strategies of Relapsing Fever Spirochetes.Frontiers in immunology · 2020Review
- To Kill But Not Be Killed: Controlling the Activity of Mammalian Pore-Forming Proteins.Frontiers in immunology · 2020Review
- Protosappanin-A and oleanolic acid protect injured podocytes from apoptosis through inhibition of AKT-mTOR signaling.Cell biology international · 2020Article
- Single-molecule kinetics of pore assembly by the membrane attack complex.Nature communications · 2019Article
- Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases.The EMBO journal · 2019Article
- The rational design of affinity-attenuated OmCI for the purification of complement C5.The Journal of biological chemistry · 2018Article
- Be on Target: Strategies of Targeting Alternative and Lectin Pathway Components in Complement-Mediated Diseases.Frontiers in immunology · 2018Review
- A Single-Domain Antibody Targeting Complement Component C5 Acts as a Selective Inhibitor of the Terminal Pathway of the Complement System and Thus Functionally Mimicks the C-Terminal Domain of theFrontiers in immunology · 2018Article
- The mystery behind membrane insertion: a review of the complement membrane attack complex.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The complement membrane attack complex (MAC) forms transmembrane pores in pathogen membranes. The first step in MAC assembly is cleavage of C5 to generate metastable C5b, which forms a stable complex with C6, termed C5b-6. C5b-6 initiates pore formation via the sequential recruitment of homologous proteins: C7, C8, and 12-18 copies of C9, each of which comprises a central MAC-perforin domain flanked by auxiliary domains. We recently proposed a model of pore assembly, in which the auxiliary domains play key roles, both in stabilizing the closed conformation of the protomers and in driving the sequential opening of the MAC-perforin β-sheet of each new recruit to the growing pore. Here, we describe an atomic model of C5b-6 at 4.2 Å resolution. We show that C5b provides four interfaces for the auxiliary domains of C6. The largest interface is created by the insertion of an interdomain linker from C6 into a hydrophobic groove created by a major reorganization of the α-helical domain of C5b. In combination with the rigid body docking of N-terminal elements of both proteins, C5b becomes locked into a stable conformation. Both C6 auxiliary domains flanking the linker pack tightly against C5b. The net effect is to induce the clockwise rigid body rotation of four auxiliary domains, as well as the opening/twisting of the central β-sheet of C6, in the directions predicted by our model to activate or prime C6 for the subsequent steps in MAC assembly. The complex also suggests novel small molecule strategies for modulating pathological MAC assembly.
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