Identification of brominated proteins in renal extracellular matrix: Potential interactions with peroxidasin

Sergey V Ivanov; Kristie L Rose; Selene Colon; Roberto M Vanacore; Billy G Hudson; Gautam Bhave; Paul Voziyan

doi:10.1016/j.bbrc.2023.09.063

Identification of brominated proteins in renal extracellular matrix: Potential interactions with peroxidasin

Biochem Biophys Res Commun. 2023 Nov 12:681:152-156. doi: 10.1016/j.bbrc.2023.09.063. Epub 2023 Sep 25.

Authors

Sergey V Ivanov¹, Kristie L Rose², Selene Colon¹, Roberto M Vanacore¹, Billy G Hudson³, Gautam Bhave⁴, Paul Voziyan⁵

Affiliations

¹ Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA; Vanderbilt Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN, 37212, USA.
² Department of Biochemistry, Vanderbilt University, Nashville, TN, 37232, USA.
³ Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA; Vanderbilt Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN, 37212, USA; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37232, USA.
⁴ Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA; Vanderbilt Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN, 37212, USA; Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
⁵ Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA; Vanderbilt Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN, 37212, USA. Electronic address: paul.voziyan@vumc.org.

PMID: 37776746
PMCID: PMC10591789 (available on 2024-11-12)
DOI: 10.1016/j.bbrc.2023.09.063

Abstract

Peroxidasin (PXDN) is an extracellular peroxidase, which generates hypobromous acid to form sulfilimine cross-links within collagen IV networks. We have previously demonstrated that mouse and human renal basement membranes (BM) are enriched in bromine due to PXDN-dependent post-translational bromination of protein tyrosine residues. The goal of the present study was identification of specific brominated sites within renal BM. A comprehensive analysis of brominated proteome of mouse glomerular matrix had been performed using liquid chromatography-tandem mass spectrometry. We found that out of over 200 identified proteins, only three were detectably brominated, each containing a single distinct brominated tyrosine site i.e., Tyr-1485 in collagen IV α2 chain, Tyr-292 in TINAGL1 and Tyr-664 in nidogen-2. To explain this highly selective bromination, we proposed that these proteins interact with PXDN within the glomerular matrix. Experiments using purified proteins demonstrated that both TINAGL1 and nidogen-2 can compete with PXDN for binding to collagen IV and that TINAGL1 can directly interact with PXDN. We propose that a protein complex, including PXDN, TINAGL1, nidogen-2 and collagen IV, may exist in renal BM.

Keywords: Bromination; Collagen IV; Extracellular matrix; Nidogen-2; Peroxidasin; TINAGL1.

Abstract

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