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Title
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ECM1 interacts with fibulin-3 and the beta 3 chain of laminin 332 through its serum albumin subdomain-like 2 domain
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Author
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Abstract
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| The extracellular matrix protein 1 (ECM1) is an 85 kDa secreted glycoprotein, comprising four variants and playing a pivotal role in endochondral bone formation, angiogenesis, and tumour biology. A computational model for the three-dimensional structure of ECM1a was determined to identify the potential and/or concealed region(s) for binding with candidate partners in human skin. Multiple alignments for the secondary structure of ECM1a and b revealed similarity with serum albumin. The N-terminal domain of ECM1a consists mainly of á-helices (áD1), while the remaining three domains, namely serum albumin subdomain-like (SASDL) domains 2-4, were topologically comparable with the subdomain of the third serum albumin domain. Yeast-two-hybrid screening of a human foreskin cDNA library using both full-length ECM1a and the hot spot region for ECM1 gene mutations in lipoid proteinosis, an autosomal recessive genodermatosis (complete SASDL2 and the linker to SASDL3: aa177aa361), as bait, isolated seven extracellular proteins. The site-specific interaction of ECM1a with two of these candidate binders, laminin 332 beta-3 chain and fibulin-3, was confirmed by in vitro and in vivo co-immunoprecipitation experiments. Immunohistologically both binders co-localized with ECM1 in human skin. Together, ECM1 is a multifunctional binding core and/or a scaffolding protein interacting with a variety of extracellular and structural proteins, contributing to the maintenance of skin integrity and homeostasis. Hence, disruption of the ECM1 function may cause the failure of multi-communication among the surrounding skin interstitial molecules, as seen in lipoid proteinosis pathology. |
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Language
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English
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Source (journal)
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Matrix biology. - Stuttgart
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Publication
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Stuttgart
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2009
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ISSN
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0945-053X
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DOI
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10.1016/J.MATBIO.2009.02.003
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Volume/pages
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28
:3
(2009)
, p. 160-169
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ISI
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000266757900005
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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