A cysteine for glycine substitution at position 175 in an alpha 1 (I) chain of type I collagen produces a clinically heterogeneous form of osteogenesis imperfecta
| Autor: | Wouter J. de Wet, Petrus J. Pretorius, Mary K. Wirtz, W. Nancy de Vries, Velidi H. Rao, David W. Hollister, Robert W. Glanville, Michael E. Labhard |
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| Rok vydání: | 1993 |
| Předmět: |
Mutant
Molecular Sequence Data Glycine Biology medicine.disease_cause Biochemistry Rheumatology medicine Humans Orthopedics and Sports Medicine Amino Acid Sequence Cysteine Structural motif Molecular Biology Chromatography High Pressure Liquid Mutation Base Sequence Cell Biology DNA Fibroblasts Middle Aged Osteogenesis Imperfecta Procollagen peptidase Phenotype Female Collagen Protein Processing Post-Translational Type I collagen Procollagen Triple helix |
| Zdroj: | Connective tissue research. 29(1) |
| ISSN: | 0300-8207 |
| Popis: | The molecular basis for Osteogenesis Imperfecta in a large kindred with a highly variable phenotype was identified by sequencing the mutant pro alpha 1 (I) protein, cDNA and genomic DNA from the proband. Fibroblasts from different affected individuals all synthesize both normal Type I procollagen molecules and abnormal Type I procollagen molecules in which one or both pro alpha 1 (I) chain(s) contain a cysteine residue within the triple helical domain. Protein studies of the proband localized the mutant cysteine residue to the alpha 1 (I) CB 8 peptide. We now report that cysteine has replaced glycine at triple helical residue 175 disrupting the invariant Gly-X-Y structural motif required for perfect triple helix formation. The consequences include post-translational overmodification, decreased thermal stability, and delayed secretion of mutant molecules. The highly variable phenotype in the present kindred cannot be explained solely on the basis of the cysteine for glycine substitution but will require further exploration. |
| Databáze: | OpenAIRE |
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