Source:http://linkedlifedata.com/resource/pubmed/id/16407265
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2006-3-6
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pubmed:abstractText |
We demonstrate that 85 N-terminal amino acids of the alpha1(I) chain participate in a highly stable folding domain, acting as the stabilizing anchor for the amino end of the type I collagen triple helix. This anchor region is bordered by a microunfolding region, 15 amino acids in each chain, which include no proline or hydroxyproline residues and contain a chymotrypsin cleavage site. Glycine substitutions and amino acid deletions within the N-anchor domain induce its reversible unfolding above 34 degrees C. The overall triple helix denaturation temperature is reduced by 5-6 degrees C, similar to complete N-anchor removal. N-propeptide partially restores the stability of mutant procollagen but not sufficiently to prevent N-anchor unfolding and a conformational change at the N-propeptide cleavage site. The ensuing failure of N-proteinase to cleave at the misfolded site leads to incorporation of pN-collagen into fibrils. Similar, but weaker, effects are caused by G88E substitution in the adjacent triplet, which appears to alter N-anchor structure as well. As in Ehlers-Danlos syndrome (EDS) VIIA/B, fibrils containing pN-collagen are thinner and weaker causing EDS-like laxity of large and small joints and paraspinal ligaments. However, distinct structural consequences of N-anchor destabilization result in a distinct alpha1(I)-osteogenesis imperfecta (OI)/EDS phenotype.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
281
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6463-70
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pubmed:meshHeading |
pubmed-meshheading:16407265-Amino Acid Sequence,
pubmed-meshheading:16407265-Calorimetry, Differential Scanning,
pubmed-meshheading:16407265-Circular Dichroism,
pubmed-meshheading:16407265-Collagen Type I,
pubmed-meshheading:16407265-Ehlers-Danlos Syndrome,
pubmed-meshheading:16407265-Humans,
pubmed-meshheading:16407265-Molecular Sequence Data,
pubmed-meshheading:16407265-Osteogenesis Imperfecta,
pubmed-meshheading:16407265-Peptide Fragments,
pubmed-meshheading:16407265-Phenotype,
pubmed-meshheading:16407265-Point Mutation,
pubmed-meshheading:16407265-Protein Denaturation,
pubmed-meshheading:16407265-Protein Folding,
pubmed-meshheading:16407265-Protein Structure, Tertiary
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pubmed:year |
2006
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pubmed:articleTitle |
Molecular mechanism of alpha 1(I)-osteogenesis imperfecta/Ehlers-Danlos syndrome: unfolding of an N-anchor domain at the N-terminal end of the type I collagen triple helix.
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pubmed:affiliation |
Section on Physical Biochemistry, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.
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pubmed:publicationType |
Journal Article
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