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

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

Research output: Contribution to journalArticle

16 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

Fingerprint

Crosslinking
Collagen
Oligomerization
Basement Membrane
Tissue
peroxidasin
Oligomers
Cysteine
Monomers
Proteins

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Structure-function analysis of peroxidasin provides insight into the mechanism of collagen IV crosslinking. / Lázár, Eniko; Péterfi, Zalán; Sirokmány, Gábor; Kovács, Hajnal A.; Klement, E.; Medzihradszky, Katalin F.; Geiszt, M.

In: Free Radical Biology and Medicine, Vol. 83, 01.06.2015, p. 273-282.

Research output: Contribution to journalArticle

Lázár, Eniko ; Péterfi, Zalán ; Sirokmány, Gábor ; Kovács, Hajnal A. ; Klement, E. ; Medzihradszky, Katalin F. ; Geiszt, M. / Structure-function analysis of peroxidasin provides insight into the mechanism of collagen IV crosslinking. In: Free Radical Biology and Medicine. 2015 ; Vol. 83. pp. 273-282.
@article{6a5480fcd0ce420cb19354a57d4dad8b,
title = "Structure-function analysis of peroxidasin provides insight into the mechanism of collagen IV crosslinking",
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.",
keywords = "Collagen IV, Crosslink, Peroxidase, Peroxidasin, Reactive oxygen species",
author = "Eniko L{\'a}z{\'a}r and Zal{\'a}n P{\'e}terfi and G{\'a}bor Sirokm{\'a}ny and Kov{\'a}cs, {Hajnal A.} and E. Klement and Medzihradszky, {Katalin F.} and M. Geiszt",
year = "2015",
month = "6",
day = "1",
doi = "10.1016/j.freeradbiomed.2015.02.015",
language = "English",
volume = "83",
pages = "273--282",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Structure-function analysis of peroxidasin provides insight into the mechanism of collagen IV crosslinking

AU - Lázár, Eniko

AU - Péterfi, Zalán

AU - Sirokmány, Gábor

AU - Kovács, Hajnal A.

AU - Klement, E.

AU - Medzihradszky, Katalin F.

AU - Geiszt, M.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

KW - Collagen IV

KW - Crosslink

KW - Peroxidase

KW - Peroxidasin

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=84928408657&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928408657&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2015.02.015

DO - 10.1016/j.freeradbiomed.2015.02.015

M3 - Article

C2 - 25708780

AN - SCOPUS:84928408657

VL - 83

SP - 273

EP - 282

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

ER -