Insights into the structure and dynamics of lysyl oxidase propeptide, a flexible protein with numerous partners
Sylvain D. Vallet , Adriana E. Miele , Urszula Uciechowska-Kaczmarzyk , Józef Adam Liwo , Bertrand Duclos , Sergey Samsonov , Sylvie Ricard-Blum
AbstractLysyl 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.
|Journal series||Scientific Reports, ISSN 2045-2322, (A 40 pkt)|
|Publication size in sheets||0.75|
|License||Journal (articles only); published final; ; with publication|
|Score|| = 40.0, 31-08-2018, ArticleFromJournal|
= 40.0, 31-08-2018, ArticleFromJournal
|Publication indicators||: 2016 = 4.259 (2) - 2016=4.847 (5)|
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