ArticleThe Journal of clinical investigation1995
Crucial residues in the carboxy-terminal end of C1 inhibitor revealed by pathogenic mutants impaired in secretion or function.
Article in The Journal of clinical investigation, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 70 citations in OpenAlex.
- Leveraging Genetics for Hereditary Angioedema: A Road Map to Precision Medicine.Clinical reviews in allergy & immunology · 2021Review
- Deep Intronic Mutation in SERPING1 Caused Hereditary Angioedema Through Pseudoexon Activation.Journal of clinical immunology · 2020Article
- Dominant-negative SERPING1 variants cause intracellular retention of C1 inhibitor in hereditary angioedema.The Journal of clinical investigation · 2019Article
- Intermittent C1-Inhibitor Deficiency Associated with Recessive Inheritance: Functional and Structural Insight.Scientific reports · 2018Article
- Hepatic fibrosis and carcinogenesis in α1-antitrypsin deficiency: a prototype for chronic tissue damage in gain-of-function disorders.Cold Spring Harbor perspectives in biology · 2011Review
- The pathophysiology of hereditary angioedema.The World Allergy Organization journal · 2010Article
- Specific interactions of serpins in their native forms attenuate their conformational transitions.Protein science : a publication of the Protein Society · 2007Article
- Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond.The Journal of allergy and clinical immunology · 2004Article
- The role of strand 1 of the C beta-sheet in the structure and function of alpha(1)-antitrypsin.Protein science : a publication of the Protein Society · 2001Article
- Angioedema associated with C1 inhibitor deficiency.Clinical reviews in allergy & immunology · 1999Review
- Exhaustive mutation scanning by fluorescence-assisted mismatch analysis discloses new genotype-phenotype correlations in angiodema.American journal of human genetics · 1996Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The last exon of the C1-1NH gene was screened for point mutations in 36 unrelated hereditary angioedema patients. Mutations were found in eight patients, predicting changes in the short COOH-terminal region which anchors the reactive site loop on its COOH-terminal side. The effects of each of these mutations were examined in transiently transfected Cos-7 cells. Complete intracellular retention or degradation was observed with substitutions in the COOH-terminal strands 4B or 5B: Leu459-->Pro, Leu459-->Arg, and Pro467-->Arg were all blocked at early stages of intracellular transport, but differences in the immunofluorescence patterns indicated that a significant fraction of the Leu459-->Pro and of the Pro467-->Arg proteins reached a compartment distinct from the endoplasmic reticulum. In line with previous findings with alpha 1-antitrypsin, chain termination within strand 5B resulted in rapid degradation. Mutant Val451-->Met, in strand 1C, and mutant Pro476-->Ser, replacing the invariant proline near the COOH terminus, yielded reduced secretion, but these extracellular proteins were unable to bind the target protease C1s. Presence of low levels of both dysfunctional proteins in patient plasmas defies the conventional classification of C1 inhibitor deficiencies as type I or type II. These data point to a key role of certain residues in the conserved COOH-terminal region of serpins in determining the protein foldings compatible with transport and proper exposure of the reactive site loop.
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