TY - JOUR AU - Holers, V. Michael T1 - Human C3 glomerulopathy provides unique insights into complement factor H–related protein function PY - 2013/06/03/ AB - 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. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI69684 VL - 123 IS - 6 UR - https://doi.org/10.1172/JCI69684 SP - 2357 EP - 2360 PB - The American Society for Clinical Investigation ER -