Interaction of Complement Defence Collagens C1q and Mannose-Binding Lectin with BMP-1/Tolloid-like Proteinases

Sci Rep. 2017 Dec 5;7(1):16958. doi: 10.1038/s41598-017-17318-w.


The defence collagens C1q and mannose-binding lectin (MBL) are immune recognition proteins that associate with the serine proteinases C1r/C1s and MBL-associated serine proteases (MASPs) to trigger activation of complement, a major innate immune system. Bone morphogenetic protein-1 (BMP-1)/tolloid-like proteinases (BTPs) are metalloproteinases with major roles in extracellular matrix assembly and growth factor signalling. Despite their different functions, C1r/C1s/MASPs and BTPs share structural similarities, including a specific CUB-EGF-CUB domain arrangement found only in these enzymes that mediates interactions with collagen-like proteins, suggesting a possible functional relationship. Here we investigated the potential interactions between the defence collagens C1q and MBL and the BTPs BMP-1 and mammalian tolloid-like-1 (mTLL-1). C1q and MBL bound to immobilized BMP-1 and mTLL-1 with nanomolar affinities. These interactions involved the collagen-like regions of the defence collagens and were inhibited by pre-incubation of C1q or MBL with their cognate complement proteinases. Soluble BMP-1 and mTLL-1 did not inhibit complement activation and the defence collagens were neither substrates nor inhibitors of BMP-1. Finally, C1q co-localized with BMP-1 in skin biopsies following melanoma excision and from patients with recessive dystrophic epidermolysis bullosa. The observed interactions provide support for a functional link between complement and BTPs during inflammation and tissue repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Bone Morphogenetic Protein 1 / genetics
  • Bone Morphogenetic Protein 1 / metabolism*
  • Complement Activation
  • Complement C1q / metabolism*
  • Epidermolysis Bullosa Dystrophica / metabolism
  • Epidermolysis Bullosa Dystrophica / pathology
  • Humans
  • Mannose-Binding Lectin / metabolism*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Tolloid-Like Metalloproteinases / metabolism*


  • Mannose-Binding Lectin
  • Complement C1q
  • Tolloid-Like Metalloproteinases
  • TLL1 protein, human
  • BMP1 protein, human
  • Bone Morphogenetic Protein 1