Substitution of cysteine for glycine-946 in the alpha 1(I) chain of type I procollagen causes lethal osteogenesis imperfecta.
Procollagen synthesized by skin fibroblasts from a patient with a lethal variant of osteogenesis imperfecta has been characterized. After pepsin digestion of the type I procollagen, a portion of the alpha 1(I) chains was recovered as a disulfide-bonded dimer. Cyanogen bromide peptide mapping suggested that a new cysteine residue was present in the alpha 1(I)CB6 fragment. Sequencing of cloned cDNAs prepared using mRNA from the proband's fibroblasts demonstrated that some of the clones contained a single base mutation that converted the glycine codon in amino acid position 946 of the alpha 1(I) chain to a cysteine codon. The thermal stability of the molecules was markedly lower than that in the case of the normal control.
Kurosaka
D
D
Department of Tissue Physiology, Tokyo Medical and Dental University.
Hattori
S
S
Hori
H
H
Yamaguchi
N
N
Hasegawa
T
T
Akimoto
H
H
Nagai
Y
Y
D001483:Base Sequence; D002478:Cells, Cultured; D003545:Cysteine / Q000235:genetics*; D004220:Disulfides; D005998:Glycine / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D008969:Molecular Sequence Data; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D011347:Procollagen / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D004220:Disulfides; D011347:Procollagen; D012333:RNA, Messenger; D003545:Cysteine; D005998:Glycine