Biological activity of ectodysplasin A is conditioned by Its collagen and heparan sulfate proteoglycan-binding domains

Lee Kim Swee, Karine Ingold-Salamin, Aubry Tardivel, Laure Willen, Olivier Gaide, Manuel Favre, Stephane Demotz, Marja Mikkola, Pascal Schneider

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    Sammanfattning

    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.
    Originalspråkengelska
    TidskriftJournal of Biological Chemistry
    Volym284
    Utgåva40
    Sidor (från-till)27567-27576
    Antal sidor10
    ISSN0021-9258
    DOI
    StatusPublicerad - 2009
    MoE-publikationstypA1 Tidskriftsartikel-refererad

    Citera det här

    Swee, L. K., Ingold-Salamin, K., Tardivel, A., Willen, L., Gaide, O., Favre, M., ... Schneider, P. (2009). Biological activity of ectodysplasin A is conditioned by Its collagen and heparan sulfate proteoglycan-binding domains. Journal of Biological Chemistry, 284(40), 27567-27576. https://doi.org/10.1074/jbc.M109.042259
    Swee, Lee Kim ; Ingold-Salamin, Karine ; Tardivel, Aubry ; Willen, Laure ; Gaide, Olivier ; Favre, Manuel ; Demotz, Stephane ; Mikkola, Marja ; Schneider, Pascal. / Biological activity of ectodysplasin A is conditioned by Its collagen and heparan sulfate proteoglycan-binding domains. I: Journal of Biological Chemistry. 2009 ; Vol. 284, Nr. 40. s. 27567-27576.
    @article{4113da9126f64ff5977627ffab547065,
    title = "Biological activity of ectodysplasin A is conditioned by Its collagen and heparan sulfate proteoglycan-binding domains",
    abstract = "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.",
    author = "Swee, {Lee Kim} and Karine Ingold-Salamin and Aubry Tardivel and Laure Willen and Olivier Gaide and Manuel Favre and Stephane Demotz and Marja Mikkola and Pascal Schneider",
    year = "2009",
    doi = "10.1074/jbc.M109.042259",
    language = "English",
    volume = "284",
    pages = "27567--27576",
    journal = "Journal of Biological Chemistry",
    issn = "0021-9258",
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    }

    Swee, LK, Ingold-Salamin, K, Tardivel, A, Willen, L, Gaide, O, Favre, M, Demotz, S, Mikkola, M & Schneider, P 2009, 'Biological activity of ectodysplasin A is conditioned by Its collagen and heparan sulfate proteoglycan-binding domains', Journal of Biological Chemistry, vol. 284, nr. 40, s. 27567-27576. https://doi.org/10.1074/jbc.M109.042259

    Biological activity of ectodysplasin A is conditioned by Its collagen and heparan sulfate proteoglycan-binding domains. / Swee, Lee Kim; Ingold-Salamin, Karine; Tardivel, Aubry; Willen, Laure; Gaide, Olivier; Favre, Manuel; Demotz, Stephane; Mikkola, Marja; Schneider, Pascal.

    I: Journal of Biological Chemistry, Vol. 284, Nr. 40, 2009, s. 27567-27576.

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    TY - JOUR

    T1 - Biological activity of ectodysplasin A is conditioned by Its collagen and heparan sulfate proteoglycan-binding domains

    AU - Swee, Lee Kim

    AU - Ingold-Salamin, Karine

    AU - Tardivel, Aubry

    AU - Willen, Laure

    AU - Gaide, Olivier

    AU - Favre, Manuel

    AU - Demotz, Stephane

    AU - Mikkola, Marja

    AU - Schneider, Pascal

    PY - 2009

    Y1 - 2009

    N2 - 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.

    AB - 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.

    U2 - 10.1074/jbc.M109.042259

    DO - 10.1074/jbc.M109.042259

    M3 - Article

    VL - 284

    SP - 27567

    EP - 27576

    JO - Journal of Biological Chemistry

    JF - Journal of Biological Chemistry

    SN - 0021-9258

    IS - 40

    ER -