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

Sofie Symoens, Marjolijn Renard, Christelle Bonod-Bidaud, Delfien Syx, Elisabeth Vaganay, Fransiska Malfait, Sylvie Ricard-Blum, Efrat Kessler, Lut Van Laer, Paul Coucke, Florence Ruggiero, Anne De Paepe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


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 coimmunoprecipitation: 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.

Original languageEnglish
Pages (from-to)371-381
Number of pages11
JournalBiochemical Journal
Issue number2
StatePublished - 15 Jan 2011


FundersFunder number
Seventh Framework Programme200647


    • Ehlers-Danlos syndrome
    • Extracellular matrix
    • Fibrillogenesis
    • Type V collagen
    • α1-N-propeptide


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