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Complement Gene Variants Define the Conformational Dynamics of C3 Convertase
Journal article   Open access   Peer reviewed

Complement Gene Variants Define the Conformational Dynamics of C3 Convertase

Héctor Martín Merinero, Seth J Welsh, Zhen Xu, Richard J H Smith and Yuzhou Zhang
European journal of immunology, Vol.56(7), e70242
07/22/2026
DOI: 10.1002/eji.70242
PMID: 42484458
url
https://doi.org/10.1002/eji.70242View
Published (Version of record) Open Access

Abstract

Current understanding of the structure, function, and molecular dynamics of the alternative pathway C3-convertase has been shaped by the clinical impact of genetic variants in complement genes. Characterizing the functional impact of different mutations not only provides patient-specific insights into the pathogenic mechanisms underlying a number of complement-mediated diseases but, at a broader level, allows us to dissect the molecular underpinnings of protein-protein interactions that drive complement amplification and its control. In this review, we contextualize over 100 variants in C3, CFB, CFD, CFH, and CFI to illustrate how this collective knowledge informs known mechanisms of complement biology and illuminates gaps that remain to be defined.
Mutation Animals Complement C3 - genetics Complement C3-C5 Convertases - chemistry Complement C3-C5 Convertases - genetics Complement C3-C5 Convertases - metabolism Complement System Proteins - genetics Genetic Variation Humans Protein Conformation UIOWA OA Agreement

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