锌绑定Tyr402和His402异型补充因子H:可能对年龄相关性黄斑变性的影响。
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南R, Farabella我,舒马赫FF,米勒,倾心于J,马丁AC,琼斯DT,阿帕德我,帕金斯SJ
锌绑定Tyr402和His402异型补充因子H:可能对年龄相关性黄斑变性的影响。
J杂志。2011年5月13日,408 (4):714 - 35。doi: 10.1016 / j.jmb.2011.03.006。Epub 2011年3月17日。
- PubMed ID
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21396937 (在PubMed]
- 文摘
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Tyr402His多态性的补因子H (FH) 20短补调节器(SCR)域与年龄相关性黄斑变性(AMD)相关联。如何跳频导致疾病病理还不清楚。跳频和高浓度的锌在点存款,AMD的关键特性。抑制了杂合的FH锌,造成总跳频。这里,锌结合纯合子的跳频进行了研究。通过分析超速离心法、大量的寡聚物观察与本机Tyr402和AMD-risk His402纯合子异型的跳频,重组SCR-6/8与酪氨酸/ His402异型。x射线散射还显示,跳频和SCR-6/8异型强烈聚合> 10妈妈锌。SCR-1/5和SCR-16/20碎片不太可能将锌。这些观察结果支持生物信息学预测。从已知的锌结合位点在晶体结构中,我们预测202年FH假定的部分表面锌结合位点,其中大多数是在SCR-6。 Metal site prediction web servers also suggested that SCR-6 and other domains bind zinc. Predicted SCR-6/8 dimer structures showed that zinc binding sites could be formed at the protein-protein interface that would lead to daisy-chained oligomers. It was concluded that zinc binds weakly to FH at multiple surface locations, most probably within the functionally important SCR-6/8 domains, and this explains why zinc inhibits FH activity. Given the high pathophysiological levels of bioavailable zinc present in subretinal deposits, we discuss how zinc binding to FH may contribute to deposit formation and inflammation associated with AMD.