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Article: Type X collagen multimer assembly in vitro is prevented by a Gly618 to Val mutation in the α1(X) NC1 domain resulting in Schmid metaphyseal chondrodysplasia

TitleType X collagen multimer assembly in vitro is prevented by a Gly618 to Val mutation in the α1(X) NC1 domain resulting in Schmid metaphyseal chondrodysplasia
Authors
Issue Date1995
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 1995, v. 270 n. 9, p. 4558-4562 How to Cite?
AbstractType X collagen is a homotrimer of α1(X) chains encoded by the COL10A1 gene. It is a highly specialized extracellular matrix component, and its synthesis is restricted to hypertrophic chondrocytes in the calcifying cartilage of the growth plate and in zones of secondary ossification. Our studies on a family with Schmid metaphyseal chondrodysplasia demonstrated that the affected individuals were heterozygous for a single base substitution in the COL10A1 gene, which changed the codon GGC for glycine 618 to GTC for valine in the highly conserved region of the carboxyl-terminal NC1 domain and altered the amino acid sequence in the putative oligosaccharide attachment site. Since hypertrophic cartilage tissue or cell cultures were not available to assess the effect of the mutation, an in vitro cDNA expression system was used to study normal and mutant type X collagen biosynthesis and assembly. Full-length cDNA constructs of the normal type X collagen sequence and also cDNA containing the specific Gly to Val NC1 mutation found in the patient were produced and expressed by in vitro transcription and translation. While the control construct produced type X collagen, which formed trimeric collagen monomers and assembled into larger multimeric assemblies, the mutant collagen was unable to form these larger aggregates. These experiments demonstrated that the mutation disturbed type X collagen NC1 domain interaction and assembly, a finding consistent with the abnormal disorganized cartilage growth plate seen in the patient. These studies provide the first evidence of the effect of a type X collagen mutation on protein structure and function and directly demonstrate the critical role of interactions between NC1 domains in the formation of type X collagen multimeric structures in vitro.
Persistent Identifierhttp://hdl.handle.net/10722/147396
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, Den_US
dc.contributor.authorCole, WGen_US
dc.contributor.authorRogers, JGen_US
dc.contributor.authorBateman, JFen_US
dc.date.accessioned2012-05-29T06:03:25Z-
dc.date.available2012-05-29T06:03:25Z-
dc.date.issued1995en_US
dc.identifier.citationJournal Of Biological Chemistry, 1995, v. 270 n. 9, p. 4558-4562en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10722/147396-
dc.description.abstractType X collagen is a homotrimer of α1(X) chains encoded by the COL10A1 gene. It is a highly specialized extracellular matrix component, and its synthesis is restricted to hypertrophic chondrocytes in the calcifying cartilage of the growth plate and in zones of secondary ossification. Our studies on a family with Schmid metaphyseal chondrodysplasia demonstrated that the affected individuals were heterozygous for a single base substitution in the COL10A1 gene, which changed the codon GGC for glycine 618 to GTC for valine in the highly conserved region of the carboxyl-terminal NC1 domain and altered the amino acid sequence in the putative oligosaccharide attachment site. Since hypertrophic cartilage tissue or cell cultures were not available to assess the effect of the mutation, an in vitro cDNA expression system was used to study normal and mutant type X collagen biosynthesis and assembly. Full-length cDNA constructs of the normal type X collagen sequence and also cDNA containing the specific Gly to Val NC1 mutation found in the patient were produced and expressed by in vitro transcription and translation. While the control construct produced type X collagen, which formed trimeric collagen monomers and assembled into larger multimeric assemblies, the mutant collagen was unable to form these larger aggregates. These experiments demonstrated that the mutation disturbed type X collagen NC1 domain interaction and assembly, a finding consistent with the abnormal disorganized cartilage growth plate seen in the patient. These studies provide the first evidence of the effect of a type X collagen mutation on protein structure and function and directly demonstrate the critical role of interactions between NC1 domains in the formation of type X collagen multimeric structures in vitro.en_US
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshChild, Preschoolen_US
dc.subject.meshCollagen - Genetics - Metabolismen_US
dc.subject.meshDnaen_US
dc.subject.meshGlycine - Genetics - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutationen_US
dc.subject.meshOsteochondrodysplasias - Geneticsen_US
dc.subject.meshValine - Genetics - Metabolismen_US
dc.titleType X collagen multimer assembly in vitro is prevented by a Gly618 to Val mutation in the α1(X) NC1 domain resulting in Schmid metaphyseal chondrodysplasiaen_US
dc.typeArticleen_US
dc.identifier.emailChan, D:chand@hkucc.hku.hken_US
dc.identifier.authorityChan, D=rp00540en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1074/jbc.270.9.4558en_US
dc.identifier.pmid7876225-
dc.identifier.scopuseid_2-s2.0-0028965555en_US
dc.identifier.volume270en_US
dc.identifier.issue9en_US
dc.identifier.spage4558en_US
dc.identifier.epage4562en_US
dc.identifier.isiWOS:A1995QK08400058-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridChan, D=7402216545en_US
dc.identifier.scopusauthoridCole, WG=7201518727en_US
dc.identifier.scopusauthoridRogers, JG=7404268782en_US
dc.identifier.scopusauthoridBateman, JF=16135557700en_US

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