Structure-function analysis of peroxidasin provides insight into the mechanism of collagen IV crosslinking

Eniko Lázár, Zalán Péterfi, Gábor Sirokmány, Hajnal A. Kovács, Eva Klement, Katalin F. Medzihradszky, Miklós Geiszt

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Basement membranes provide structural support and convey regulatory signals to cells in diverse tissues. Assembly of collagen IV into a sheet-like network is a fundamental mechanism during the formation of basement membranes. Peroxidasin (PXDN) was recently described to catalyze crosslinking of collagen IV through the formation of sulfilimine bonds. Despite the significance of this pathway in tissue genesis, our understanding of PXDN function is far from complete. In this work we demonstrate that collagen IV crosslinking is a physiological function of mammalian PXDN. Moreover, we carried out structure-function analysis of PXDN to gain a better insight into its role in collagen IV synthesis. We identify conserved cysteines in PXDN that mediate the oligomerization of the protein into a trimeric complex. We also demonstrate that oligomerization is not an absolute requirement for enzymatic activity, but optimal collagen IV coupling is only catalyzed by the PXDN trimers. Localization experiments of different PXDN mutants in two different cell models revealed that PXDN oligomers, but not monomers, adhere on the cell surface in "hot spots," which represent previously unknown locations of collagen IV crosslinking.

Original languageEnglish
Pages (from-to)273-282
Number of pages10
JournalFree Radical Biology and Medicine
Volume83
DOIs
Publication statusPublished - Jun 1 2015

Keywords

  • Collagen IV
  • Crosslink
  • Peroxidase
  • Peroxidasin
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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