Purpose: To report a novel L558P mutation of the human transforming growth factor β-induced (TGFBI) gene found in Ukrainian families with atypical corneal dystrophy (CD). Methods: Genomic DNA was extracted from peripheral leukocytes of 12 members of 4 unrelated families with atypical CD. We performed genotype analysis of these families with microsatellite markers surrounding the TGFBI locus. Exons of the TGFBI gene were amplified by polymerase chain reaction (PCR), and directly sequenced in 5 patients of 4 unrelated families. We utilized a simple PCR/restriction fragment length polymorphism-based technique for L558P mutation identification. Fifty normal individuals were also analyzed as controls. These assays were complemented by histological analysis of available corneal buttons excised during penetrating keratoplasty. Results: A heterozygous single-base-pair transition (CTC to CCC, leucine to proline) at codon 558 in exon 12 of the TGFBI gene (L558P) was detected in 10 individuals. Eight are affected, and 2 are teenagers with no clinical manifestation of the disease as yet. The mutation was not found in 2 healthy individuals from 2 high-risk CD families, nor in 50 normal controls. Histopathological examination identified amyloid deposits, mostly in the posterior central cornea. Haplotype analysis provided evidence of a common founder of the L558P mutation. The mutation works on the protein level by disrupting an α-helix, which is crucial for the normal functioning of keratoepithelin. Conclusion: A novel L558P mutation in the TGFBI gene causes an atypical type of stromal CD.

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Проведен поиск элементов структурной организации белка ЫО, которые необходимы для взаимодействия этого белка с мРНКовыми мишенями, лежащего в основе выпол нения белком ЫО функции аутогенной регуляции экспрессии генов rplJL энтеробактерий. Во взаимодействии с мРНКовыми мишенями у энтеробактерий могут участвовать следующие структурные элементы ЫО: мотив-kNTll-, мотив-Eif-и структура альфа-бета-альфа (98-111).

Here we report a study of molecular dynamics of a YCD2 fragment of mammalian tyrosyl-tRNA synthethase (Asp322-Ser528), which includes the COOH-terminal cytokine-like domain, intermodular flexible linker, and H5-a-helix of catalytic core of synthetase. Our calculations show that while compact C-terminal domain was less flexible and relatively stable, the interdomain linker shows a high degree of conformational changes. After short relaxation time it forms a short helix-like structure, which may be involved in the regulation of domain interaction and modulation of protein activities.