Mechanism of the very efficient quenching of tryptophan fluorescence in human gamma D- and gamma S-crystallins: the gamma-crystallin fold may have evolved to protect tryptophan residues from ultraviolet photodamage.
Mechanism of the very efficient quenching of tryptophan fluorescence in human gamma D- and gamma S-crystallins: the gamma-crystallin fold may have evolved to protect tryptophan residues from ultraviolet photodamage.
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DOI：
10.1021/bi802177g
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发表时间：
2009-05-05
期刊：
影响因子：
2.9
通讯作者：
King, Jonathan
中科院分区：
文献类型：
--
作者：
Chen, Jiejin;Callis, Patrik R.;King, Jonathan
暴露于紫外线辐射的蛋白质会通过色氨酸（Trps）和其他紫外线吸收氨基酸的共价修饰而受到不可逆转的光损伤。晶状体蛋白是维持透镜透明度的脊椎动物眼透镜的主要蛋白质组分，在整个生命过程中暴露于环境UV辐射。人类和所有其他脊椎动物中的β-和γ-晶状体蛋白的重复β-折叠希腊关键结构域各自具有两个保守的埋藏Trp。实验和计算表明，通过静电使能电子转移到骨架酰胺，人γ D-晶状体蛋白中这些Trps的荧光在天然状态下被非常有效地淬灭[Chen et al.（2006）Biochemistry 45，11552−11563]。预期激发态能量的这种分散将使来自激发的Trp环的共价断裂的蛋白质损伤最小化。我们在这里报告的实验和计算表明，相同的快速电子转移机制是在不同的晶体蛋白，人类γ S-晶体蛋白。对其他晶体蛋白的解析结构的研究表明，Trp构象，以及有利取向的结合沃茨，以及在淬灭的Trp（残基n）之前的n − 3个残基的骨架羰基氧的邻近性，在大多数晶体蛋白中是保守的。这些结果表明，快速电荷转移淬灭是这种蛋白质折叠的进化特性，可能保护它免受紫外线诱导的光损伤。这种紫外线抗性可能有助于选择希腊关键折叠作为所有脊椎动物中的主要透镜蛋白。
Proteins exposed to UV radiation are subject to irreversible photodamage through covalent modification of tryptophans (Trps) and other UV-absorbing amino acids. Crystallins, the major protein components of the vertebrate eye lens that maintain lens transparency, are exposed to ambient UV radiation throughout life. The duplicated β-sheet Greek key domains of β- and γ-crystallins in humans and all other vertebrates each have two conserved buried Trps. Experiments and computation showed that the fluorescence of these Trps in human γD-crystallin is very efficiently quenched in the native state by electrostatically enabled electron transfer to a backbone amide [Chen et al. (2006) Biochemistry 45, 11552−11563]. This dispersal of the excited state energy would be expected to minimize protein damage from covalent scission of the excited Trp ring. We report here both experiments and computation showing that the same fast electron transfer mechanism is operating in a different crystallin, human γS-crystallin. Examination of solved structures of other crystallins reveals that the Trp conformation, as well as favorably oriented bound waters, and the proximity of the backbone carbonyl oxygen of the n − 3 residues before the quenched Trps (residue n), are conserved in most crystallins. These results indicate that fast charge transfer quenching is an evolved property of this protein fold, probably protecting it from UV-induced photodamage. This UV resistance may have contributed to the selection of the Greek key fold as the major lens protein in all vertebrates.
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影响因子：
4.1
作者：
Chen, CW;Roy, D
通讯作者：
Roy, D
影响因子：
2
作者：
GROSSWEINER, LI
通讯作者：
GROSSWEINER, LI
影响因子：
2.8
作者：
Callis, PR;Vivian, JT
通讯作者：
Vivian, JT
影响因子：
2.9
作者：
Kurz, LC;Fite, B;Callis, P
通讯作者：
Callis, P
影响因子：
4.2
作者：
BACHEM, A
通讯作者：
BACHEM, A