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Human C3 glomerulopathy provides unique insights into complement factor H-related protein function.

Authors
Type
Published Article
Journal
Journal of Clinical Investigation
1558-8238
Publisher
American Society for Clinical Investigation
Publication Date
Volume
123
Issue
6
Pages
2357–2360
Identifiers
PMID: 23728171
Source
Medline
License
Unknown

Abstract

The study in this issue of the JCI by Tortajada et al. demonstrates that a duplication within the gene complement factor H–related 1 (CFHR1; encoding FHR1) leads to the production of an aberrant larger form of the protein. Elegant in vitro studies of the mutant and normal variants demonstrate an unexpected mechanism of action of FHR1, wherein homodimeration and hetero- oligomerization with FHR2 and FHR5 generates more avid molecules that very effectively compete with FH binding to surfaces and impair its ability to regulate local complement activation. As variants of FHRs are linked to many human inflammatory and autoimmune diseases, these and other recently published structure/function studies of these proteins provide key insights into their complement regulatory activities and likely roles in disease.

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