Source:http://linkedlifedata.com/resource/pubmed/id/19657145
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
40
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| pubmed:dateCreated |
2009-10-5
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| pubmed:abstractText |
Mutations in the TNF family ligand EDA1 cause X-linked hypohidrotic ectodermal dysplasia (XLHED), a condition characterized by defective development of skin appendages. The EDA1 protein displays a proteolytic processing site responsible for its conversion to a soluble form, a collagen domain, and a trimeric TNF homology domain (THD) that binds the receptor EDAR. In-frame deletions in the collagen domain reduced the thermal stability of EDA1. Removal of the collagen domain decreased its activity about 100-fold, as measured with natural and engineered EDA1-responsive cell lines. The collagen domain could be functionally replaced by multimerization domains or by cross-linking antibodies, suggesting that it functions as an oligomerization unit. Surprisingly, mature soluble EDA1 containing the collagen domain was poorly active when administered in newborn, EDA-deficient (Tabby) mice. This was due to a short stretch of basic amino acids located at the N terminus of the collagen domain that confers EDA1 with proteoglycan binding ability. In contrast to wild-type EDA1, EDA1 with mutations in this basic sequence was a potent inducer of tail hair development in vivo. Thus, the collagen domain activates EDA1 by multimerization, whereas the proteoglycan-binding domain may restrict the distribution of endogeneous EDA1 in vivo.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Ectodysplasins,
http://linkedlifedata.com/resource/pubmed/chemical/Heparan Sulfate Proteoglycans,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Ectodysplasin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
1083-351X
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
2
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| pubmed:volume |
284
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
27567-76
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| pubmed:dateRevised |
2010-10-5
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| pubmed:meshHeading |
pubmed-meshheading:19657145-Amino Acid Sequence,
pubmed-meshheading:19657145-Animals,
pubmed-meshheading:19657145-Antibodies,
pubmed-meshheading:19657145-Cell Death,
pubmed-meshheading:19657145-Cell Line,
pubmed-meshheading:19657145-Collagen,
pubmed-meshheading:19657145-Cross-Linking Reagents,
pubmed-meshheading:19657145-Ectodysplasins,
pubmed-meshheading:19657145-Embryonic Development,
pubmed-meshheading:19657145-Gene Expression Regulation,
pubmed-meshheading:19657145-Genetic Engineering,
pubmed-meshheading:19657145-Hair,
pubmed-meshheading:19657145-Heparan Sulfate Proteoglycans,
pubmed-meshheading:19657145-Humans,
pubmed-meshheading:19657145-Keratinocytes,
pubmed-meshheading:19657145-Mice,
pubmed-meshheading:19657145-NF-kappa B,
pubmed-meshheading:19657145-Protein Multimerization,
pubmed-meshheading:19657145-Protein Structure, Quaternary,
pubmed-meshheading:19657145-Protein Structure, Tertiary,
pubmed-meshheading:19657145-Receptors, Ectodysplasin,
pubmed-meshheading:19657145-Tail
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| pubmed:year |
2009
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| pubmed:articleTitle |
Biological activity of ectodysplasin A is conditioned by its collagen and heparan sulfate proteoglycan-binding domains.
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| pubmed:affiliation |
Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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