Molecular basis of subtotal complement C6 deficiency. A carboxy-terminally truncated but functionally active C6

The Journal of Clinical Investigation
Reinhard WürznerP J Lachmann

Abstract

Individuals with subtotal complement C6 deficiency possess a C6 molecule that is 14% shorter than normal C6 and present in low but detectable concentrations (1-2% of the normal mean). We now show that this dysmorphic C6 is bactericidally active and lacks an epitope that was mapped to the most carboxy-terminal part of C6 using C6 cDNA fragments expressed as fusion proteins in the pUEX expression system. We thus predicted that the abnormal C6 molecule might be carboxy-terminally truncated and sought a mutation in an area approximately 14% from the carboxy-terminal end of the coding sequence. By sequencing PCR-amplified products from this region, we found, in three individuals from two families, a mutation that might plausibly be responsible for the defect. All three have an abnormal 5' splice donor site of intron 15, which would probably prevent splicing. An in-frame stop codon is found 17 codons downstream from the intron boundary, which would lead to a truncated polypeptide 13.5% smaller than normal C6. This result was unexpected, as earlier studies mapped the C5b binding site, or a putative enzymatic region, to this part of C6. Interestingly, all three subjects were probably heterozygous for both subtotal C6 and complete C6 de...Continue Reading

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Citations

Oct 12, 2010·Clinical Microbiology Reviews·Sanjay RamPeter A Rice
Jan 1, 2014·Molecular Immunology·Dineke WestraAdilia Warris
Jun 2, 2009·Molecular Immunology·Marina BottoFrancesco Tedesco
Jun 1, 2011·Molecular Immunology·Lillemor SkattumLennart Truedsson
Apr 4, 2017·The Journal of Infectious Diseases·Jérémie RosainVéronique Frémeaux-Bacchi
Apr 5, 2007·European Journal of Immunology·Marie-Anne Rameix-WeltiVeronique Frémeaux-Bacchi
Dec 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Jean-Laurent Casanova
Nov 5, 1999·The Journal of Biological Chemistry·R G DiScipioN K Rushmere
Dec 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chuong-Thu Thai, Ronald T Ogata
Sep 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chuong-Thu Thai, Ronald T Ogata
May 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chuong-Thu Thai, Ronald T Ogata
Feb 19, 2020·Human Genetics·Stephanie HodeibVanessa Sancho-Shimizu
Jul 19, 2003·Clinical and Experimental Immunology·M F Vázquez-BermúdezB Sánchez
Mar 26, 2003·Clinical and Experimental Immunology·M A Dragon-DureyM D Kazatchkine
Nov 24, 2004·Immunology·Sonia BarrosoAntonio Núñez-Roldán

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