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Pathogenic Mutations in a Human Mitochondrial Enzyme Affect Protein Stability
Author(s) -
Kennicott Hannah,
McCurdy Clara,
Makori Jessica,
Chihade Joseph
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.630.5
Subject(s) - proteolysis , protein stability , mutant , mutation , enzyme , biology , mitochondrial disease , biochemistry , mitochondrion , microbiology and biotechnology , genetics , mitochondrial dna , gene
Mutations in human mitochondrial alanyl tRNA‐synthetase have been correlated with at least two different pathologies, infantile cardiomyopathy and leukodystrophy. We have used a bacterial expression system to study the effects of these mutations on protein stability. All mutations tested lead to reduced amounts of full‐length soluble enzyme. Several render the protein insoluble, while others lead to proteolysis into soluble or insoluble fragments. Correlations between protein stability and disease state will be presented. We are currently investigating whether the addition of solubility tags will reverse these effects and facilitate the purification of full‐length mutants. Support or Funding Information Carleton College and the Towsley Foundation This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .