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||Repository; published final; ; with publication|
|Score||= 40.0, 21-02-2020, ArticleFromJournal|
|Publication indicators||= 3; = 6; : 2016 = 1.401; : 2018 = 4.011 (2) - 2018=4.525 (5)|
|Citation count*||6 (2020-02-13)|
|Licencja||Utwór jest udostępniany na licencji Creative Commons Uznanie autorstwa 4.0 Międzynarodowe (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/d|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.