ECM1 interacts with fibulin-3 and the beta 3 chain of laminin 332 through its serum albumin subdomain-like 2 domain.
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 alpha-helices (alphaD1), 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: aa177-aa361), 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.
Sercu
S
S
Laboratory of Molecular Biotechnology, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium.
Lambeir
A M
AM
Steenackers
E
E
El Ghalbzouri
A
A
Geentjens
K
K
Sasaki
T
T
Oyama
N
N
Merregaert
J
J
D000595:Amino Acid Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002474:Cell-Free System / Q000378:metabolism; D002478:Cells, Cultured; D004817:Epidermis / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D015603:Keratinocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012709:Serum Albumin / Q000235:genetics; D012867:Skin / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D014809:Vitamin D-Binding Protein / Q000235:genetics; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D011994:Recombinant Proteins; D012709:Serum Albumin; D014809:Vitamin D-Binding Protein; D000097794:Kalinin; C490607:ECM1 protein, human; C119630:EFEMP1 protein, human