Protein primary structure correlates with calcium oxalate stone matrix preference.
Protein primary structure correlates with calcium oxalate stone matrix preference.
复制标题
DOI：
10.1371/journal.pone.0257515
复制
发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Wesson JA
中科院分区：
文献类型：
--
作者：
Tian Y;Tirrell M;Davis C;Wesson JA
尽管基质蛋白在草酸钙肾结石形成中具有明显的重要性，但蛋白质混合物的复杂性仍然难以解释。基于一系列的实验，我们提出了一个模型，蛋白质聚集体形成的混合物含有强电荷的聚阴离子和强电荷的聚阳离子可以启动草酸钙晶体的形成和晶体聚集，创造一个石头。这些蛋白质聚集体还优先从尿液中吸附许多弱电荷蛋白质，以产生模拟患者样品中观察到的蛋白质分布的复杂蛋白质混合物。为了验证这个模型的基本细节，并确定在弱电荷蛋白质中观察到的相选择性的解释，我们已经检查了主要蛋白质的一级结构，这些蛋白质更喜欢基质相或尿相的天冬氨酸、谷氨酸、赖氨酸和精氨酸的含量;这些氨基酸在正常尿液pH值为6 - 7时代表固定电荷。我们验证了富含大量带电残基的蛋白质在结石基质中的富集，这些残基表现出极端的等电点，低（pI <5）和高（pI> 9）。我们发现，许多蛋白质与中间等电点表现出偏好结石基质含有较少数量的电荷残基，虽然仍然更多的总电荷比中间等电点蛋白质更喜欢尿相。虽然其他来源的电荷尚未被考虑，蛋白质的石基质的偏好似乎与高总电荷含量。
Despite the apparent importance of matrix proteins in calcium oxalate kidney stone formation, the complexity of the protein mixture continues to elude explanation. Based on a series of experiments, we have proposed a model where protein aggregates formed from a mixture containing both strongly charged polyanions and strongly charged polycations could initiate calcium oxalate crystal formation and crystal aggregation to create a stone. These protein aggregates also preferentially adsorb many weakly charged proteins from the urine to create a complex protein mixture that mimics the protein distributions observed in patient samples. To verify essential details of this model and identify an explanation for phase selectivity observed in weakly charged proteins, we have examined primary structures of major proteins preferring either the matrix phase or the urine phase for their contents of aspartate, glutamate, lysine and arginine; amino acids that would represent fixed charges at normal urine pH of 6–7. We verified enrichment in stone matrix of proteins with a large number of charged residues exhibiting extreme isoelectric points, both low (pI<5) and high (pI>9). We found that the many proteins with intermediate isoelectric points exhibiting preference for stone matrix contained a smaller number of charge residues, though still more total charges than the intermediate isoelectric point proteins preferring the urine phase. While other sources of charge have yet to be considered, protein preference for stone matrix appears to correlate with high total charge content.
登录
查看更多内容
影响因子：
3.7
作者：
Aggarwal KP;Tandon S;Naik PK;Singh SK;Tandon C
通讯作者：
Tandon C
DOI：
10.1152/ajprenal.00134.2008
发表时间：
2008-10-01
影响因子：
4.2
作者：
Merchant, Michael L.;Cummins, Timothy D.;Lederer, Eleanor D.
通讯作者：
Lederer, Eleanor D.
影响因子：
--
作者：
Viswanathan, Pragasam;Rimer, Jeffrey D.;Kolbach, Ann M.;Ward, Michael D.;Kleinman, Jack G.;Wesson, Jeffrey A.
通讯作者：
Wesson, Jeffrey A.
影响因子：
--
作者：
Wesson, JA;Ganne, V;Kleinman, JG
通讯作者：
Kleinman, JG
影响因子：
3.1
作者：
Berger GK;Eisenhauer J;Vallejos A;Hoffmann B;Wesson JA
通讯作者：
Wesson JA