Functional expression of human mutant phosphofructokinase in yeast: genetic defects in French Canadian and Swiss patients with phosphofructokinase deficiency
| Autor: | N, Raben, R, Exelbert, R, Spiegel, J B, Sherman, H, Nakajima, P, Plotz, J, Heinisch |
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| Rok vydání: | 1995 |
| Předmět: |
Adult
Male Canada Protein Denaturation Glycogen Storage Disease Type VII Hot Temperature Base Sequence Phosphofructokinase-1 Recombinant Fusion Proteins Molecular Sequence Data Saccharomyces cerevisiae Catalysis Enzyme Induction Humans Point Mutation Female France Alleles Switzerland Research Article |
| Zdroj: | American journal of human genetics. 56(1) |
| ISSN: | 0002-9297 |
| Popis: | Human phosphofructokinase (PFK) is a tetrameric enzyme, encoded by muscle, liver, and platelet genes. Deficiency of muscle PFK (PFK-M), glycogenosis type VII (Tarui disease), is an autosomal recessive disorder characterized by an exertional myopathy and hemolytic syndrome. Several disease-causing mutations have been identified in the PFK-M gene in Japanese, Ashkenazi Jewish, and Italian patients. We describe the genetic defects in French Canadian and Swiss patients with the disease, and we use a genetically well-defined yeast system devoid of endogenous PFK for structure-function studies of the mutant PFKs. A G-to-A transition at codon 209-in exon 8 of the PFK-M gene, changing an encoded Gly to Asp, is responsible for the disease in a homozygous French Canadian patient. Gly-209-mutated protein is completely inactive in the yeast system. The Swiss patient is a genetic compound, carrying a G-to-A transition at codon 100 in exon 6 (Arg to Gln) and a G-to-A transition at codon 696 in exon 22 (Arg to His). The mutants expressed in yeast generate functional enzyme with modest changes in thermal stability. The advantages and limitations of the yeast system for expression of human mutant PFKs are discussed. |
| Databáze: | OpenAIRE |
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