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Journal articles

Insights into the structure and dynamics of lysyl oxidase propeptide, a flexible protein with numerous partners

Abstract : Lysyl oxidase (LOX) catalyzes the oxidative deamination of lysine and hydroxylysine residues in collagens and elastin, which is the first step of the cross-linking of these extracellular matrix proteins. It is secreted as a proenzyme activated by bone morphogenetic protein-1, which releases the LOX catalytic domain and its bioactive N-terminal propeptide. We characterized the recombinant human propeptide by circular dichroism, dynamic light scattering, and small-angle X-ray scattering (SAXS), and showed that it is elongated, monomeric, disordered and flexible (D max : 11.7 nm, R g : 3.7 nm). We generated 3D models of the propeptide by coarse-grained molecular dynamics simulations restrained by SAXS data, which were used for docking experiments. Furthermore, we have identified 17 new binding partners of the propeptide by label-free assays. They include four glycosaminoglycans (hyaluronan, chondroitin, dermatan and heparan sulfate), collagen I, cross-linking and proteolytic enzymes (lysyl oxidase-like 2, transglutaminase-2, matrix metalloproteinase-2), a proteoglycan (fibromodulin), one growth factor (Epidermal Growth Factor, EGF), and one membrane protein (tumor endothelial marker-8). This suggests new roles for the propeptide in EGF signaling pathway.
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Sylvain Vallet, Adriana Miele, Urszula Uciechowska-Kaczmarzyk, Adam Liwo, Bertrand Duclos, et al.. Insights into the structure and dynamics of lysyl oxidase propeptide, a flexible protein with numerous partners. Scientific Reports, Nature Publishing Group, 2018, 8 (1), pp.122-149. ⟨10.1038/s41598-018-30190-6⟩. ⟨hal-02109680⟩



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