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

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.
Author Sylvain D. Vallet - [Institut de Chimie et Biochimie Moléculaire et Supramoléculaire]
Sylvain D. Vallet,,
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, Adriana E. Miele - [Institut de Chimie et Biochimie Moléculaire et Supramoléculaire]
Adriana E. Miele,,
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, Urszula Uciechowska-Kaczmarzyk (FCh / DTCh / LMM)
Urszula Uciechowska-Kaczmarzyk,,
- Laboratory of Molecular Modeling
, Józef Adam Liwo (FCh / DTCh / LMM)
Józef Adam Liwo,,
- Laboratory of Molecular Modeling
, Bertrand Duclos - [Institut de Chimie et Biochimie Moléculaire et Supramoléculaire]
Bertrand Duclos,,
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, Sergey Samsonov (FCh / DTCh / LMM)
Sergey Samsonov,,
- Laboratory of Molecular Modeling
, Sylvie Ricard-Blum - [Institut de Chimie et Biochimie Moléculaire et Supramoléculaire]
Sylvie Ricard-Blum,,
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Journal seriesScientific Reports, ISSN 2045-2322, (A 40 pkt)
Issue year2018
Vol8
Pages1-16
Publication size in sheets0.75
Article number11768
ASJC Classification1000 Multidisciplinary
DOIDOI:10.1038/s41598-018-30190-6
URL https://www.nature.com/articles/s41598-018-30190-6
Languageen angielski
LicenseRepository; published final; Uznanie Autorstwa (CC-BY); with publication
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Vallet_Sylvain_Insights_into_the_structure_and_dynamics_of_lysyl_oxidase_propeptid,_a_flexible_protein_with_numerous_partners_2018.pdf 2.89 MB
Score (nominal)40
Score sourcejournalList
ScoreMinisterial score = 40.0, 21-02-2020, ArticleFromJournal
Publication indicators WoS Citations = 3; Scopus Citations = 6; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 1.401; WoS Impact Factor: 2018 = 4.011 (2) - 2018=4.525 (5)
Citation count*6 (2020-02-13)
Additional fields
LicencjaUtwór jest udostępniany na licencji Creative Commons Uznanie autorstwa 4.0 Międzynarodowe (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/d
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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