The structure of human complement component C7 and the C5b-7 complex.

DiScipio, Richard G.; Chakravarti, Deb N.; Müller‐Eberhard, Hans J.; Fey, G H

doi:10.1016/s0021-9258(19)57427-0

Cited by 182 publications

(35 citation statements)

References 52 publications

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“…Upon production, C5b associates with C6, forming the soluble C5b6 complex (Cooper and M€ uller-Eberhard, 1970). Addition of C7 generates C5b67, denoted as C5b-7, which adheres to membranes (DiScipio et al, 1988;Preissner et al, 1985). Association of the heterotrimeric C8abg yields C5b-8, which forms small pores with a 0.9-nm diameter and, as time progresses, generates 3-nm pores (Ramm et al, 1982;Zalman and M€ uller-Eberhard, 1990).…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous MAC Initiator and Pore Structures in a Lipid Bilayer by Phase-Plate Cryo-electron Tomography

2016

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Pore formation in membranes is important for mammalian immune defense against invading bacteria. Induced by complement activation, the membrane attack complex (MAC) forms through sequential binding and membrane insertion of C5b6, C7, C8, and C9. Using cryo-electron tomography with a Volta phase plate and subtomogram averaging, we imaged C5b-7, C5b-8, and C5b-9 complexes and determined the C5b-9 pore structure in lipid bilayers. The in situ C5b-9 pore structure at 2.3-nm resolution reveals a 10- to 11.5-nm cone-shaped pore starting with C5b678 and multiple copies of C9 that is poorly closed, yielding a seam between C9 and C6 substituting for the shorter β strands in C6 and C7. However, large variations of composite pore complexes are apparent in subtomograms. Oligomerized initiator complexes C5b-7 and C5b-8 show stages of membrane binding, deformation, and perforation that yield ∼3.5-nm-wide pores. These data indicate a dynamic process of pore formation that likely adapts to biological membranes under attack.

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Section: Introductionmentioning

confidence: 99%

Heterogeneous MAC Initiator and Pore Structures in a Lipid Bilayer by Phase-Plate Cryo-electron Tomography

2016

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“…34 This protein initiates membrane attack complex formation by binding the C5b-C6 subcomplex and inserts into the phospholipid bilayer, serving as a membrane anchor. 35 A previous study showed that C7 might be a potential tumor suppressor. 36 C7 is also a critical component of the terminal pathway of complement activation.…”

Section: Discussionmentioning

confidence: 99%

“… 36 C7 is also a critical component of the terminal pathway of complement activation. 35 C7 is expressed in endothelial cells as a trap for assembling MACs. MAC deposition has been reported in smooth muscle, 37 dermatomyositis microvasculature 38 , 39 and in the mechanism of advanced diabetic kidney disease.…”

Section: Discussionmentioning

confidence: 99%

Complement C7 is Specifically Expressed in Mesangial Cells and is a Potential Diagnostic Biomarker for Diabetic Nephropathy and is Regulated by miR-494-3p and miR-574-5p

Guo¹,

Yan²,

Hu³

et al. 2021

DMSO

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Background: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, but it remains relatively underdiagnosed. Objective: In this study, we aimed to explore the key regulatory pathways and potential biomarkers related to DN using integrated bioinformatics analysis and validation. Methods: First, the microarray data of the GSE30528 and GSE96804 datasets were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were screened. Then, weighted gene coexpression network analysis (WGCNA), gene ontology (GO) annotation, gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify key pathways and genes. qRT-PCR and receiver operating characteristic (ROC) curves were used to validate our results. Furthermore, single-cell RNA sequencing (scRNA-seq) data were reanalyzed to investigate the expression specificity of C7 in DN cells. An online database search and luciferase reporter assay identified the target relationship between miRNAs and C7. Results: The "complement and coagulation cascades" were significantly enriched, and complement C3 and C7 were candidate markers. The receiver operating characteristic (ROC) curve revealed that C7 had significant diagnostic value (AUC=0.865) in DN. Through scRNA-seq reanalysis, we found that C7 was specifically elevated in mesangial (MES) cells of DN. Moreover, we found that the expression of C7 was regulated by miR-494-3p and miR-574-5p. Conclusion: This is the first study to reveal that C7 is specifically expressed in mesangial cells, is a potential diagnostic biomarker for diabetic nephropathy, and is regulated by miR-494-3p and miR-574-5p.

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“…PS exposure further increased as a result of the formation of C5b-7 and was most significant following C5b-8 complexes formation after the incubation of RBCs with IgM aab and C8-or C9-depleted serum, respectively. C5b-7 complexes adhere to the cell membrane [31,32] and induce the generation of ceramide as well as Ca 2+ influx, which are principal mediators of eryptosis [7,8,[32][33][34][35][36]. Hence, PS exposure at this stage may be due to Ca 2+ influx.…”

Section: Discussionmentioning

confidence: 99%

Sublytic Terminal Complement Components Induce Eryptosis in Autoimmune Haemolytic Anaemia Related to IgM Autoantibodies

2019

Cell Physiol Biochem

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The structure of human complement component C7 and the C5b-7 complex.

Cited by 182 publications

References 52 publications

Heterogeneous MAC Initiator and Pore Structures in a Lipid Bilayer by Phase-Plate Cryo-electron Tomography

Heterogeneous MAC Initiator and Pore Structures in a Lipid Bilayer by Phase-Plate Cryo-electron Tomography

Complement C7 is Specifically Expressed in Mesangial Cells and is a Potential Diagnostic Biomarker for Diabetic Nephropathy and is Regulated by miR-494-3p and miR-574-5p

Sublytic Terminal Complement Components Induce Eryptosis in Autoimmune Haemolytic Anaemia Related to IgM Autoantibodies

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