Peroxidasin-mediated bromine enrichment of basement membranes

Significance Bromine is an essential trace element, required for the formation of sulfilimine cross-links in collagen IV, a basement membrane protein. Sulfilimine cross-link formation depends on the production of hypobromous acid by peroxidasin. Once the cross-links are formed, bromide is released, but we suspected that hypobromous acid might brominate bystander molecules in the basement membrane. NanoSIMS imaging of mouse kidneys revealed peroxidasin-dependent bromine enrichment in the basement membrane, and proteomics studies uncovered peroxidasin-dependent bromination of a specific tyrosine in collagen IV. Our studies show that bromine, an essential element, is largely restricted to basement membranes in mammalian tissues. Our studies also show that peroxidasin brominates bystander tyrosines in addition to promoting the formation of collagen IV sulfilimine cross-links.