Letter to the Editor:: 1H, 15N and 13C resonance assignment of human γS-crystallin, a 21 kDa eye-lens protein
Letter to the Editor:: 1H, 15N and 13C resonance assignment of human γS-crystallin, a 21 kDa eye-lens protein
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DOI：
10.1007/s10858-004-3497-3
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发表时间：
2004-11-01
影响因子：
2.7
通讯作者：
Lequin, O
中科院分区：
文献类型：
--
作者：
Baraguey, C;Skouri-Panet, H;Lequin, O
白内障是眼晶状体的浑浊化，其通常是由于其称为晶状体蛋白的本体结构蛋白的年龄相关改变（Bloemendal等人，2004年）。这些蛋白质在保持透镜的光学性质方面起着核心作用，并且由于它们需要持续使用寿命，因此具有异常的稳定性。它们分为两个主要家族，a-晶体蛋白，其属于小的热休克蛋白超家族，和B/c晶体蛋白，由两个b-三明治结构域组成，每个结构域包含两个希腊关键基序。cS-晶状体蛋白是成年哺乳动物透镜的主要成分。与cA-cF对应物相比，它的关系更远，并且在透镜内的时空表达也不同。它缺乏温度诱导的混浊，通常观察到其他c-晶体蛋白和称为冷性白内障。cS-晶状体蛋白对氧化特别敏感，氧化被认为有助于白内障（Skouri-Panet等人，2001年）。此外，已经发现小鼠cS-晶状体蛋白基因的几种突变是白内障的原因（Sinha等人，2001; Bu等人，2002年）。尽管已知几种b-和c-晶体蛋白的X射线结构，但迄今为止全长cS-晶体蛋白对结晶具有抗性。仅确定了人和牛cS-晶状体蛋白的C-末端结构域的晶体结构（Basak等人，1998; Purkiss等人，2002）。我们启动了对人类cS-晶状体蛋白的核磁共振研究，以研究溶液中全长蛋白质的结构和两个结构域之间的相互作用。由于残基Cys 24显示在温和氧化条件下参与二聚体形成（Skouri-Panet et al.，2001），对C24 S突变体进行NMR研究。
Cataract is an opacification of the eye-lens, which is often due to age-related alterations of its bulk structural proteins called crystallins (Bloemendal et al., 2004). These proteins play a central role in maintaining the optical properties of the lens and are characterized by an exceptional stability since they need to last a life time. They fall into two major families, a-crystallins, which belong to the small heat-shock protein superfamily, and b/ccrystallins, consisting of two b-sandwich domains, each containing two Greek key motifs. cS-crystallin is a major component of the adult mammalian lens. It is more distantly related compared to its cA-cF counterparts and also differs by its spatio-temporal expression within the lens. It lacks the temperature-induced opacification typically observed with other c-crystallins and known as cold cataract. cS-crystallin is especially sensitive to oxidation, which is thought to contribute to cataract (Skouri-Panet et al., 2001). Furthermore, several mutations of the mouse cS-crystallin gene have been found to be responsible for cataract (Sinha et al., 2001; Bu et al., 2002). Although the X-ray structures of several b-and c-crystallins are known, full length cS-crystallin has been resistant to crystallisation so far. Only the crystal structures of the C-terminal domain of human and bovine cS-crystallins have been determined (Basak et al., 1998; Purkiss et al., 2002).We have initiated an NMR study of human cS-crystallin to investigate the structure and the interactions between the two domains in the context of the full length protein in solution. Since residue Cys24 was shown to be involved in dimer formation under mild oxidative conditions (Skouri-Panet et al., 2001), the NMR study was carried out on a C24S mutant.