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Complement System

Complement System

The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a membrane...

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Related Experiment Video

Updated: Jul 11, 2026

Enrichment of Bruch's Membrane from Human Donor Eyes

Enrichment of Bruch's Membrane from Human Donor Eyes

Published on: November 15, 2015

Structural basis for complement factor H linked age-related macular degeneration.

Beverly E Prosser¹, Steven Johnson, Pietro Roversi

¹Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, England, UK.

The Journal of Experimental Medicine

|September 26, 2007

Summary

Age-related macular degeneration (AMD) affects millions. A common genetic risk factor involves a change in factor H (FH), a complement regulator. This study reveals how this change impacts FH

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Last Updated: Jul 11, 2026

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Area of Science:

Biochemistry
Genetics
Structural Biology

Background:

Age-related macular degeneration (AMD) is a leading cause of vision loss, affecting nearly 50 million people globally.
A significant risk factor for AMD is a specific single-nucleotide polymorphism in the factor H (FH) gene, resulting in a Tyr402His substitution.
Factor H regulates the complement system, and its localization to cell surfaces is mediated by glycosaminoglycans (GAGs).

Purpose of the Study:

To elucidate the molecular mechanism by which the Tyr402His polymorphism in factor H contributes to AMD risk.
To understand the structural basis of GAG binding to factor H and how the polymorphism affects this interaction.

Main Methods:

X-ray crystallography was used to determine the structure of the FH region containing His402 in complex with a GAG analogue.
Structure-based site-directed mutagenesis was performed to investigate the functional consequences of the polymorphism.
Nuclear magnetic resonance (NMR) spectroscopy was employed to monitor binding interactions of FH variants with GAGs.

Main Results:

The crystal structure revealed direct coordination of the GAG ligand by the polymorphic His402 residue.
This interaction site is centrally located within an extended groove, suggesting multivalent GAG binding.
Mutagenesis and NMR binding studies confirmed the differential interaction of His402 and Tyr402 variants with GAGs, providing a molecular basis for the genetic association with AMD.

Conclusions:

The Tyr402His polymorphism in factor H directly influences GAG binding, offering a molecular explanation for its link to AMD.
The identified GAG-binding site on FH is crucial for complement regulation and cell surface localization.
These findings provide critical insights into AMD pathogenesis and potential therapeutic strategies targeting the complement system.