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C-reactive protein (CRP) recognizes uric acid crystals and recruits proteases C1 and MASP1.
Scientific Reports ( IF 3.8 ) Pub Date : 2020-04-14 , DOI: 10.1038/s41598-020-63318-8
Anika Alberts 1 , Annika Klingberg 1 , Anne Kathrin Wessig 1 , Christèle Combes 2 , Torsten Witte 3 , Korbinian Brand 1 , Andreas Pich 4 , Konstantin Neumann 1
Affiliation  

Gout is caused by crystallization of uric acid in the form of monosodium urate (MSU) crystals, which induce a sterile inflammatory response that is hardly distinguishable from microbe-induced inflammatory responses. It is unclear, if MSU crystals (like microbes) are recognized by specific pattern recognition receptors. To identify possible soluble pattern recognition molecules for MSU crystals, we purified MSU-binding proteins from human body fluids. We identified C-reactive protein (CRP) as a major MSU-binding protein. Binding of CRP was strong enough to specifically deplete CRP from human serum. We found that CRP was required for fixation of complement components C1q, C1r, C1s and MASP1. Thus, we have identified a pattern recognition molecule for MSU crystals that links to the activation of complement. Notably, CRP does not show an even binding to the complete surface of the crystals. It rather binds to edges or distinct faces of the crystals.

中文翻译:

C反应蛋白(CRP)识别尿酸晶体并募集蛋白酶C1和MASP1。

痛风是由尿酸单钠盐(MSU)晶体形式的尿酸结晶引起的,这种结晶引起无菌的炎症反应,很难与微生物引起的炎症反应区分开。尚不清楚MSU晶体(如微生物)是否被特定的模式识别受体识别。为了识别MSU晶体的可能的可溶性模式识别分子,我们从人体液中纯化了MSU结合蛋白。我们确定C反应蛋白(CRP)为主要的MSU结合蛋白。CRP的结合强度足以从人血清中特异性消耗CRP。我们发现CRP是固定补体成分C1q,C1r,C1s和MASP1所必需的。因此,我们已经确定了MSU晶体的模式识别分子,该分子与补体的激活有关。值得注意的是 CRP没有显示出与晶体完整表面的均匀结合。而是绑定到晶体的边缘或不同的表面。
更新日期:2020-04-14
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