The leucine-rich repeat domain of human peroxidasin 1 promotes binding to laminin in basement membranes

Research output: Contribution to journalJournal articlepeer-review

Documents

Human peroxidasin 1 (PXDN) is a homotrimeric multidomain heme peroxidase and essential for tissue development and architecture. It has a biosynthetic function and catalyses the hypobromous acid-mediated formation of specific covalent sulfilimine (S[dbnd]N) bonds, which cross-link type IV collagen chains in basement membranes. Currently, it is unknown whether and which domain(s) [i.e. leucine-rich repeat domain (LRR), immunoglobulin domains, peroxidase domain, von Willebrand factor type C domain] of PXDN interact with the polymeric networks of the extracellular matrix (ECM), and how these interactions integrate and regulate the enzyme's cross-linking activity, without imparting oxidative damage to the ECM. In this study, we probed the interactions of four PXDN constructs with different domain compositions with components of a basement membrane extract by immunoprecipitation. Strong binding of the LRR-containing construct was detected with the major ECM protein laminin. Analysis of these interactions by surface plasmon resonance spectroscopy revealed similar kinetics and affinities of binding of the LRR-containing construct to human and murine laminin-111, with calculated dissociation constants of 1.0 and 1.5 μM, respectively. The findings are discussed with respect to the recently published in-solution structures of the PXDN constructs and the proposed biological role of this peroxidase.

Original languageEnglish
Article number108443
JournalArchives of Biochemistry and Biophysics
Volume689
Number of pages7
ISSN0003-9861
DOIs
Publication statusPublished - 15 Aug 2020

    Research areas

  • Basement membrane, Extracellular matrix, Human peroxidasin 1, Immunoprecipitation, Laminin, Surface plasmon resonance spectroscopy, Type-IV collagen

Number of downloads are based on statistics from Google Scholar and www.ku.dk


No data available

ID: 243999528