Terminal complexes of the complement system: New structural insights and their relevance to function
Abstract
Summary: Complement is a key component of innate immunity in health and a powerful driver of inflammation and tissue injury in disease. The biological and pathological effects of complement activation are mediated by activation products. These come in two flavors: (i) proteolytic fragments of complement proteins (C3, C4, C5) generated during activation that bind specific receptors on target cells to mediate effects; (ii) the multimolecular membrane attack complex generated from the five terminal complement proteins that directly binds to and penetrates target cell membranes. Several recent publications have described structural insights that have changed perceptions of the nature of this membrane attack complex. This review will describe these recent advances in understanding of the structure of the membrane attack complex and its by‐product the fluid‐phase terminal complement complex and relate these new structural insights to functional consequences and cell responses to complement membrane attack.
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Sublytic levels of MAC have been shown to stimulate the release of growth factors from nucleated cells, including VEGF from RPE in cell culture studies.
“For example, sublytic levels of MAC have been shown to stimulate the release of growth factors from nucleated cells [99,100], including VEGF from RPE in cell culture studies [146,165].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [99]
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References 95 · Cited by 58
- Authors
- Morgan, B. P., Walters, D., Serna, M., & Bubeck, D.
- Affiliations
- Cardiff University (GB)
- Imperial College London (GB)
- Corresponding author
- Morgan, Bryan Paul
- Venue
- Immunological Reviews
- Publisher
- Wiley
- Published
- 2016-10-26
- Volume
- 274
- Issue
- 1
- Pages
- 141-151
- ISSN
- 0105-2896 (ISSN-L)
- 1600-065X
- OpenAlex
- W2523592271
- Cited by
- 58
- References
- 95
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 7 · 2022: 4 · 2021: 7 · 2020: 10 · 2019: 9 · 2018: 5 · 2017: 6 · 2016: 1
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Immunological Reviews (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- Cancer Research UK (C26409/A16099)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Keywords
- complement system, membrane attack complex, complement activation, complement receptors, innate immunity, inflammation
- MeSH terms
- Animals, Cell Membrane, Complement System Proteins, Complement Activation, Humans, Immunity, Innate, Protein Conformation, Structure-Activity Relationship, Complement Membrane Attack Complex
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