Incorporation of type I collagen molecules that contain a mutant α2(I) chain (Gly580 → Asp) into bone matrix in a lethal case of osteogenesis imperfecta

C. Niyibizi, J. Bonadio, P. H. Byers, D. R. Eyre

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

To understand more directly the tissue defect in osteogenesis imperfecta (OI), bone matrix was analyzed from an infant with lethal OI (type II) of defined mutation (collagen α2(I)Gly580 → Asp). Pepsin-solubilized α1(I) and α2(I) chains and derived CNBr-peptides migrated more slowly on sodium dodecyl sulfate-polyacrylamide gel electrophoresis compared with normal human controls. The peptide α2(I)CB3,5, predicted to contain the mutation site, ran as a retarded doublet band and was purified by high performance liquid chromatography and digested with V8 protease. Two peptides with amino- terminal sequences beginning at residue 576 of the α2(I) chain were isolated. One had the normal sequence. The other differed in that aspartic acid replaced glycine at residue 580 as predicted from cDNA analysis, and in having an unhydroxylated proline at residue 579. From yields on microsequencing and the relative intensities of the two forms of α2(I)CB3,5 on SDS-polyacrylamide gel electrophoresis, the ratio of mutant to normal α2(I) chains in the infant's bone matrix was 0.7/1. Although the effects of an efficient incorporation of mutant chains on the properties of the bone matrix are unknown, it may be that in this OI case the tissue abnormalities result more from the presence of mutant protein than from an underexpression of matrix.

Original languageEnglish (US)
Pages (from-to)23108-23112
Number of pages5
JournalJournal of Biological Chemistry
Volume267
Issue number32
StatePublished - Jan 1 1992

Fingerprint

Osteogenesis Imperfecta
Bone Matrix
Viperidae
Collagen Type I
Bone
Electrophoresis
Peptides
Molecules
Polyacrylamide Gel Electrophoresis
Tissue
Mutation
Pepsin A
High performance liquid chromatography
Mutant Proteins
Proline
Aspartic Acid
Sodium Dodecyl Sulfate
Glycine
Collagen
Complementary DNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

@article{3fd74b9354be4f79a56a7c17d2651e00,
title = "Incorporation of type I collagen molecules that contain a mutant α2(I) chain (Gly580 → Asp) into bone matrix in a lethal case of osteogenesis imperfecta",
abstract = "To understand more directly the tissue defect in osteogenesis imperfecta (OI), bone matrix was analyzed from an infant with lethal OI (type II) of defined mutation (collagen α2(I)Gly580 → Asp). Pepsin-solubilized α1(I) and α2(I) chains and derived CNBr-peptides migrated more slowly on sodium dodecyl sulfate-polyacrylamide gel electrophoresis compared with normal human controls. The peptide α2(I)CB3,5, predicted to contain the mutation site, ran as a retarded doublet band and was purified by high performance liquid chromatography and digested with V8 protease. Two peptides with amino- terminal sequences beginning at residue 576 of the α2(I) chain were isolated. One had the normal sequence. The other differed in that aspartic acid replaced glycine at residue 580 as predicted from cDNA analysis, and in having an unhydroxylated proline at residue 579. From yields on microsequencing and the relative intensities of the two forms of α2(I)CB3,5 on SDS-polyacrylamide gel electrophoresis, the ratio of mutant to normal α2(I) chains in the infant's bone matrix was 0.7/1. Although the effects of an efficient incorporation of mutant chains on the properties of the bone matrix are unknown, it may be that in this OI case the tissue abnormalities result more from the presence of mutant protein than from an underexpression of matrix.",
author = "C. Niyibizi and J. Bonadio and Byers, {P. H.} and Eyre, {D. R.}",
year = "1992",
month = "1",
day = "1",
language = "English (US)",
volume = "267",
pages = "23108--23112",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "32",

}

Incorporation of type I collagen molecules that contain a mutant α2(I) chain (Gly580 → Asp) into bone matrix in a lethal case of osteogenesis imperfecta. / Niyibizi, C.; Bonadio, J.; Byers, P. H.; Eyre, D. R.

In: Journal of Biological Chemistry, Vol. 267, No. 32, 01.01.1992, p. 23108-23112.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Incorporation of type I collagen molecules that contain a mutant α2(I) chain (Gly580 → Asp) into bone matrix in a lethal case of osteogenesis imperfecta

AU - Niyibizi, C.

AU - Bonadio, J.

AU - Byers, P. H.

AU - Eyre, D. R.

PY - 1992/1/1

Y1 - 1992/1/1

N2 - To understand more directly the tissue defect in osteogenesis imperfecta (OI), bone matrix was analyzed from an infant with lethal OI (type II) of defined mutation (collagen α2(I)Gly580 → Asp). Pepsin-solubilized α1(I) and α2(I) chains and derived CNBr-peptides migrated more slowly on sodium dodecyl sulfate-polyacrylamide gel electrophoresis compared with normal human controls. The peptide α2(I)CB3,5, predicted to contain the mutation site, ran as a retarded doublet band and was purified by high performance liquid chromatography and digested with V8 protease. Two peptides with amino- terminal sequences beginning at residue 576 of the α2(I) chain were isolated. One had the normal sequence. The other differed in that aspartic acid replaced glycine at residue 580 as predicted from cDNA analysis, and in having an unhydroxylated proline at residue 579. From yields on microsequencing and the relative intensities of the two forms of α2(I)CB3,5 on SDS-polyacrylamide gel electrophoresis, the ratio of mutant to normal α2(I) chains in the infant's bone matrix was 0.7/1. Although the effects of an efficient incorporation of mutant chains on the properties of the bone matrix are unknown, it may be that in this OI case the tissue abnormalities result more from the presence of mutant protein than from an underexpression of matrix.

AB - To understand more directly the tissue defect in osteogenesis imperfecta (OI), bone matrix was analyzed from an infant with lethal OI (type II) of defined mutation (collagen α2(I)Gly580 → Asp). Pepsin-solubilized α1(I) and α2(I) chains and derived CNBr-peptides migrated more slowly on sodium dodecyl sulfate-polyacrylamide gel electrophoresis compared with normal human controls. The peptide α2(I)CB3,5, predicted to contain the mutation site, ran as a retarded doublet band and was purified by high performance liquid chromatography and digested with V8 protease. Two peptides with amino- terminal sequences beginning at residue 576 of the α2(I) chain were isolated. One had the normal sequence. The other differed in that aspartic acid replaced glycine at residue 580 as predicted from cDNA analysis, and in having an unhydroxylated proline at residue 579. From yields on microsequencing and the relative intensities of the two forms of α2(I)CB3,5 on SDS-polyacrylamide gel electrophoresis, the ratio of mutant to normal α2(I) chains in the infant's bone matrix was 0.7/1. Although the effects of an efficient incorporation of mutant chains on the properties of the bone matrix are unknown, it may be that in this OI case the tissue abnormalities result more from the presence of mutant protein than from an underexpression of matrix.

UR - http://www.scopus.com/inward/record.url?scp=0026488378&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026488378&partnerID=8YFLogxK

M3 - Article

C2 - 1385413

AN - SCOPUS:0026488378

VL - 267

SP - 23108

EP - 23112

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 32

ER -