The Ancient Immunoglobulin Domains of Peroxidasin Are Required to Form Sulfilimine Cross-links in Collagen IV
The Ancient Immunoglobulin Domains of Peroxidasin Are Required to Form Sulfilimine Cross-links in Collagen IV
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DOI：
10.1074/jbc.m115.673996
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发表时间：
2015-08-28
影响因子：
4.8
通讯作者：
Bhave, Gautam
中科院分区：
文献类型：
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作者：
Ero-Tolliver, Isi A.;Hudson, Billy G.;Bhave, Gautam
工作背景：因为过氧化物酶产生HOBr以在胶原IV中形成硫亚胺交联，所以任何产生HOBr的过氧化物酶都可以交联胶原IV。结果：在动物过氧化物酶，只有过氧化物酶有效地交联胶原IV需要其催化和免疫球蛋白结构域。结论：过氧化物酶独特地将HOBr与胶原IV反应以催化硫亚胺键的形成。重要性：深入了解过氧化物酶如何交联胶原蛋白IV是理解基底膜功能的关键。胶原蛋白IV硫亚胺交联及其催化酶，过氧化物酶，代表了组织发育的关键，这是整个动物王国保守的二分体。过氧化物酶在相对的甲硫氨酸和羟基赖氨酸残基之间形成新型硫亚胺键，以在结构上增强胶原IV支架，这是基底膜和组织完整性的关键功能。然而，交联形成的分子机制仍不清楚。在这项工作中，我们证明，过氧化物酶和免疫球蛋白（IG）结构域的催化域是必需的有效的硫亚胺键形成。因此，这些分子特征是过氧化物酶在组织发育和完整性中的进化保守功能的基础，并将过氧化物酶与其他过氧化物酶如髓过氧化物酶（MPO）和嗜酸性粒细胞过氧化物酶（EPO）区分开来。
Background: Because peroxidasin generates HOBr to form sulfilimine cross-links in collagen IV, any peroxidase producing HOBr may cross-link collagen IV. Results: Among animal peroxidases, only peroxidasin efficiently cross-linked collagen IV requiring its catalytic and immunoglobulin domains. Conclusion: Peroxidasin uniquely reacts HOBr with collagen IV to catalyze sulfilimine bond formation. Significance: Insight into how peroxidasin cross-links collagen IV is critical to understand basement membrane function.The collagen IV sulfilimine cross-link and its catalyzing enzyme, peroxidasin, represent a dyad critical for tissue development, which is conserved throughout the animal kingdom. Peroxidasin forms novel sulfilimine bonds between opposing methionine and hydroxylysine residues to structurally reinforce the collagen IV scaffold, a function critical for basement membrane and tissue integrity. However, the molecular mechanism underlying cross-link formation remains unclear. In this work, we demonstrate that the catalytic domain of peroxidasin and its immunoglobulin (Ig) domains are required for efficient sulfilimine bond formation. Thus, these molecular features underlie the evolutionarily conserved function of peroxidasin in tissue development and integrity and distinguish peroxidasin from other peroxidases, such as myeloperoxidase (MPO) and eosinophil peroxidase (EPO).