We recently discovered that the collagen IV scaffolds of bovine, mouse, and Drosophila melanogaster tissues are stabilized by sulfilimine chemical bonds (S = N) (20⇓–22). The bond is a covalent cross-link between methionine-93 (Met93) and lysine-211 or hydroxylysine-211 (Lys211/Hyl211) residues that stabilizes the noncollagenous (NC1) interface of adjoining triple helical protomers (Fig. 1A). Peroxidasin, an animal heme peroxidase embedded in basement membrane, forms these sulfilimine cross-links by producing hypohalous acids as intermediates for Met93 oxidization (21, 22). Here, we explored whether the sulfilimine cross-link of collagen IV is a fundamental requirement in the genesis and evolution of tissues in Eumetazoa. We show the cnidarian origin and essentiality of the sulfilimine cross-link in tissue development and the cnidarian origin of the paradoxical anabolic function of hypohalous acids in tissue genesis.
Aaron L. Fidler, Roberto M. Vanacore, Sergei V. Chetyrkin, Vadim K. Pedchenko, Gautam Bhave, Viravuth P. Yin, Cody L. Stothers, Kristie Lindsey Rose, W. Hayes McDonald, Travis A. Clark, Dorin-Bogdan Borza, Robert E. Steele, Michael T. Ivy, The Aspirnauts, Julie K. Hudson, Billy G. Hudson "A triad in the ECM essential for tissue evolution", Proceedings of the National Academy of Sciences Jan 2014, 111 (1) 331-336; DOI: 10.1073/pnas.1318499111