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Identification of binding partners interacting with the α1-N-propeptide of type V collagen

(2011) BIOCHEMICAL JOURNAL. 433(2). p.371-381
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Abstract
The predominant form of type V collagen is the [α1(V)]₂α2(V) heterotrimer. Mutations in COL5A1 or COL5A2, encoding respectively the α1(V)- and α2(V)-collagen chain, cause classic EDS (Ehlers-Danlos syndrome), a heritable connective tissue disorder, characterized by fragile hyperextensible skin and joint hypermobility. Approximately half of the classic EDS cases remain unexplained. Type V collagen controls collagen fibrillogenesis through its conserved α1(V)-N-propeptide domain. To gain an insight into the role of this domain, a yeast two-hybrid screen among proteins expressed in human dermal fibroblasts was performed utilizing the N-propeptide as a bait. We identified 12 interacting proteins, including extracellular matrix proteins and proteins involved in collagen biosynthesis. Eleven interactions were confirmed by surface plasmon resonance and/or co-immunoprecipitation: α1(I)- and α2(I)-collagen chains, α1(VI)-, α2(VI)- and α3(VI)-collagen chains, tenascin-C, fibronectin, PCPE-1 (procollagen C-proteinase enhancer-1), TIMP-1 (tissue inhibitor of metalloproteinases-1), MMP-2 (matrix metalloproteinase 2) and TGF-β1 (transforming growth factor β1). Solid-phase binding assays confirmed the involvement of the α1(V)-N-propeptide in the interaction between native type V collagen and type VI collagen, suggesting a bridging function of this protein complex in the cell-matrix environment. Enzymatic studies showed that processing of the α1(V)-N-propeptide by BMP-1 (bone morphogenetic protein 1)/procollagen C-proteinase is enhanced by PCPE-1. These interactions are likely to be involved in extracellular matrix homoeostasis and their disruption could explain the pathogenetic mechanism in unresolved classic EDS cases.
Keywords
Ehlers-Danlos syndrome, alpha 1-N-propeptide, extracellular matrix, fibrillogenesis, type V collagen, BONE MORPHOGENETIC PROTEIN-1, PROCOLLAGEN C-PROTEINASE, FIBRILLAR PROCOLLAGENS, EXTRACELLULAR-MATRIX, INTERACTION NETWORK, TGF-BETA, TYPES-I, COL5A1, FIBROBLASTS

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Citation

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Chicago
Symoens, Sofie, Marjolijn Renard, Christelle Bonod-Bidaud, Delfien Syx, Elisabeth Vaganay, Fransiska Malfait, Sylvie Ricard-Blum, et al. 2011. “Identification of Binding Partners Interacting with the α1-N-propeptide of Type V Collagen.” Biochemical Journal 433 (2): 371–381.
APA
Symoens, Sofie, Renard, M., Bonod-Bidaud, C., Syx, D., Vaganay, E., Malfait, F., Ricard-Blum, S., et al. (2011). Identification of binding partners interacting with the α1-N-propeptide of type V collagen. BIOCHEMICAL JOURNAL, 433(2), 371–381.
Vancouver
1.
Symoens S, Renard M, Bonod-Bidaud C, Syx D, Vaganay E, Malfait F, et al. Identification of binding partners interacting with the α1-N-propeptide of type V collagen. BIOCHEMICAL JOURNAL. 2011;433(2):371–81.
MLA
Symoens, Sofie, Marjolijn Renard, Christelle Bonod-Bidaud, et al. “Identification of Binding Partners Interacting with the α1-N-propeptide of Type V Collagen.” BIOCHEMICAL JOURNAL 433.2 (2011): 371–381. Print.
@article{1141189,
  abstract     = {The predominant form of type V collagen is the [α1(V)]₂α2(V) heterotrimer. Mutations in COL5A1 or COL5A2, encoding respectively the α1(V)- and α2(V)-collagen chain, cause classic EDS (Ehlers-Danlos syndrome), a heritable connective tissue disorder, characterized by fragile hyperextensible skin and joint hypermobility. Approximately half of the classic EDS cases remain unexplained. Type V collagen controls collagen fibrillogenesis through its conserved α1(V)-N-propeptide domain. To gain an insight into the role of this domain, a yeast two-hybrid screen among proteins expressed in human dermal fibroblasts was performed utilizing the N-propeptide as a bait. We identified 12 interacting proteins, including extracellular matrix proteins and proteins involved in collagen biosynthesis. Eleven interactions were confirmed by surface plasmon resonance and/or co-immunoprecipitation: α1(I)- and α2(I)-collagen chains, α1(VI)-, α2(VI)- and α3(VI)-collagen chains, tenascin-C, fibronectin, PCPE-1 (procollagen C-proteinase enhancer-1), TIMP-1 (tissue inhibitor of metalloproteinases-1), MMP-2 (matrix metalloproteinase 2) and TGF-β1 (transforming growth factor β1). Solid-phase binding assays confirmed the involvement of the α1(V)-N-propeptide in the interaction between native type V collagen and type VI collagen, suggesting a bridging function of this protein complex in the cell-matrix environment. Enzymatic studies showed that processing of the α1(V)-N-propeptide by BMP-1 (bone morphogenetic protein 1)/procollagen C-proteinase is enhanced by PCPE-1. These interactions are likely to be involved in extracellular matrix homoeostasis and their disruption could explain the pathogenetic mechanism in unresolved classic EDS cases.},
  author       = {Symoens, Sofie and Renard, Marjolijn and Bonod-Bidaud, Christelle and Syx, Delfien and Vaganay, Elisabeth and Malfait, Fransiska and Ricard-Blum, Sylvie and Kessler, Efrat and Van Laer, Lut and Coucke, Paul and Ruggiero, Florence and De Paepe, Anne},
  issn         = {0264-6021},
  journal      = {BIOCHEMICAL JOURNAL},
  keywords     = {Ehlers-Danlos syndrome,alpha 1-N-propeptide,extracellular matrix,fibrillogenesis,type V collagen,BONE MORPHOGENETIC PROTEIN-1,PROCOLLAGEN C-PROTEINASE,FIBRILLAR PROCOLLAGENS,EXTRACELLULAR-MATRIX,INTERACTION NETWORK,TGF-BETA,TYPES-I,COL5A1,FIBROBLASTS},
  language     = {eng},
  number       = {2},
  pages        = {371--381},
  title        = {Identification of binding partners interacting with the α1-N-propeptide of type V collagen},
  url          = {http://dx.doi.org/10.1042/BJ20101061},
  volume       = {433},
  year         = {2011},
}

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