English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/96650
Compartir / Impacto:
Estadísticas
Add this article to your Mendeley library MendeleyBASE
Citado 71 veces en Web of Knowledge®  |  Pub MebCentral Ver citas en PubMed Central  |  Ver citas en Google académico
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar otros formatos: Exportar EndNote (RIS)Exportar EndNote (RIS)Exportar EndNote (RIS)
Título

C3 glomerulopathy-associated CFHR1 mutation alters FHR oligomerization and complement regulation

Autor Tortajada, Agustín ; Yébenes, Hugo; Anter, Jauoad; García-Fernández, Jesús; Martínez-Barricarte, Rubén ; Llorca, Óscar ; Rodríguez de Córdoba, Santiago
Palabras clave Complement
C3
CFHR1
Factor H-related
Glomerulopathy
Fecha de publicación jun-2013
EditorAmerican Society for Clinical Investigation
Citación Journal of Clinical Investigation 123 (6):2434–2446 (2013)
ResumenC3 glomerulopathies (C3G) are a group of severe renal diseases with distinct patterns of glomerular inflammation and C3 deposition caused by complement dysregulation. Here we report the identification of a familial C3G-associated genomic mutation in the gene complement factor H-related 1 (CFHR1), which encodes FHR1. The mutation resulted in the duplication of the N-terminal short consensus repeats (SCRs) that are conserved in FHR2 and FHR5. We determined that native FHR1, FHR2, and FHR5 circulate in plasma as homo- and hetero-oligomeric complexes, the formation of which is likely mediated by the conserved N-terminal domain. In mutant FHR1, duplication of the N-terminal domain resulted in the formation of unusually large multimeric FHR complexes that exhibited increased avidity for the FHR1 ligands C3b, iC3b, and C3dg and enhanced competition with complement factor H (FH) in surface plasmon resonance (SPR) studies and hemolytic assays. These data revealed that FHR1, FHR2, and FHR5 organize a combinatorial repertoire of oligomeric complexes and demonstrated that changes in FHR oligomerization influence the regulation of complement activation. In summary, our identification and characterization of a unique CFHR1 mutation provides insights into the biology of the FHRs and contributes to our understanding of the pathogenic mechanisms underlying C3G. Copyright © 2013, American Society for Clinical Investigation.
Descripción Tortajada, Agustín et alt.
Versión del editorhttp://dx.doi.org/10.1172/JCI68280
URI http://hdl.handle.net/10261/96650
DOI10.1172/JCI68280
ISSN0021-9738
Aparece en las colecciones: (CIB) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
JCI 123 (6) 2013-Óscar Llorca.pdf4,07 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 



NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.