ArticleThe Journal of biological chemistry2012
Structure of complement C6 suggests a mechanism for initiation and unidirectional, sequential assembly of membrane attack complex (MAC).
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 46 papers.
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Who cites it
46 citing papers in PubMed, 105 citations in OpenAlex.
- Molecular mechanism of pore formation by Plasmodium Perforin-like Protein 2.Nature communications · 2026Article
- From a single C-mannose to multiple C-mannosyltransferases.The Journal of biological chemistry · 2026Review
- Identification of coagulation-related biomarkers in osteoarthritis and immune infiltration analysis based on bioinformatics.Hereditas · 2025Article
- Action of the Terminal Complement Pathway on Cell Membranes.The Journal of membrane biology · 2025Review
- The Complement System.Advances in experimental medicine and biology · 2025Review
- Two different complement Factor B (Bf) alleles of the orangutan major histocompatibility complex (MHC) are also conserved in chimpanzee and humans showing importance in primate immunity.Molecular biology reports · 2024Article
- Evidence of a Lytic Pathway in an Invertebrate Complement System: Identification of a Terminal Complement Complex Gene in a Colonial Tunicate and Its Evolutionary Implications.International journal of molecular sciences · 2024Article
- Evaluation of a proteomic signature coupled with the kidney failure risk equation in predicting end stage kidney disease in a chronic kidney disease cohort.Clinical proteomics · 2024Article
- Complement System Proteins in the Human Aqueous Humor and Their Association with Primary Open-Angle Glaucoma.Journal of personalized medicine · 2023Article
- Structural basis of soluble membrane attack complex packaging for clearance.Nature communications · 2021Article
- ProteinMolecules (Basel, Switzerland) · 2021Review
- Selective cross-linking of coinciding protein assemblies by in-gel cross-linking mass spectrometry.The EMBO journal · 2021Article
- How Structures of Complement Complexes Guide Therapeutic Design.Sub-cellular biochemistry · 2021Review
- Article
- To Kill But Not Be Killed: Controlling the Activity of Mammalian Pore-Forming Proteins.Frontiers in immunology · 2020Review
- Perforin-Like Proteins of Apicomplexan Parasites.Frontiers in cellular and infection microbiology · 2020Review
- Article
- Structure-function characterization of an insecticidal protein GNIP1Aa, a member of an MACPF and β-tripod families.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The first transmembrane region of complement component-9 acts as a brake on its self-assembly.Nature communications · 2018Article
- Immunohistochemical and Molecular Investigations Show Alteration in the Inflammatory Profile of Multiple System Atrophy Brain.Journal of neuropathology and experimental neurology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The complement membrane attack complex (MAC) is formed by the sequential assembly of C5b with four homologous proteins as follows: one copy each of C6, C7, and C8 and 12-14 copies of C9. Together these form a lytic pore in bacterial membranes. C6 through C9 comprise a MAC-perforin domain flanked by 4-9 "auxiliary" domains. Here, we report the crystal structure of C6, the first and longest of the pore proteins to be recruited by C5b. Comparisons with the structures of the C8αβγ heterodimer and perforin show that the central domain of C6 adopts a "closed" (perforin-like) state that is distinct from the "open" conformations in C8. We further show that C6, C8α, and C8β contain three homologous subdomains ("upper," "lower," and "regulatory") related by rotations about two hinge points. In C6, the regulatory segment includes four auxiliary domains that stabilize the closed conformation, inhibiting release of membrane-inserting elements. In C8β, rotation of the regulatory segment is linked to an opening of the central β-sheet of its clockwise partner, C8α. Based on these observations, we propose a model for initiation and unidirectional propagation of the MAC in which the auxiliary domains play key roles: in the assembly of the C5b-8 initiation complex; in driving and regulating the opening of the β-sheet of the MAC-performin domain of each new recruit as it adds to the growing pore; and in stabilizing the final pore. Our model of the assembled pore resembles those of the cholesterol-dependent cytolysins but is distinct from that recently proposed for perforin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.