Altered dynamics in Lck SH3 upon binding to the LBD1 domain of Herpesvirus saimiri Tip.
Altered dynamics in Lck SH3 upon binding to the LBD1 domain of Herpesvirus saimiri Tip.
复制标题
与疱疹病毒 saimiri Tip 的 LBD1 结构域结合后，Lck SH3 的动力学发生改变。
DOI：
10.1110/ps.052016406
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Engen,JohnR
中科院分区：
文献类型：
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作者：
Weis,DavidD;Kjellen,Peter;Sefton,BartholomewM;Engen,JohnR
来自松鼠猴疱疹病毒的Tip蛋白与来自Src家族激酶Lck的SH 3结构域通过称为LBD 1的含脯氨酸序列相互作用。与Lck相关的Src家族激酶SH 3结构域已被证明在溶液中是动态的，并且在生理条件下部分解折叠。这种部分解折叠的速率被病毒蛋白结合所降低。为了确定Lck SH 3结构域是否表现出类似的行为，使用氢交换和质谱法研究了该结构域。Lck SH 3在溶液中是高度动态的。虽然其他SH 3结构域需要多达10，000秒才能完全氘化，但Lck SH 3在200秒内几乎完全标记。观察到涉及8-10个残基的部分解折叠事件，半衰期为10秒。提示LBD 1结合没有引起Lck SH 3的总体结构变化，但全局稳定了结构域，并将部分解折叠的速率降低了5倍。发现Lck SH 3中部分解折叠的区域与部分解折叠的其他SH 3结构域所鉴定的区域相似。虽然Lck SH 3和其他密切相关的SH 3结构域之间的序列保守性很高，但动态似乎并不保守。
The Tip protein fromHerpesvirus saimiriinteracts with the SH3 domain from the Src‐family kinase Lck via a proline‐containing sequence termed LBD1. Src‐family kinase SH3 domains related to Lck have been shown to be dynamic in solution and partially unfold under physiological conditions. The rate of such partial unfolding is reduced by viral protein binding. To determine if the Lck SH3 domain displayed similar behavior, the domain was investigated with hydrogen exchange and mass spectrometry. Lck SH3 was found to be highly dynamic in solution. While other SH3 domains require as much as 10,000 sec to become totally deuterated, Lck SH3 became almost completely labeled within 200 sec. A partial unfolding event involving 8–10 residues was observed with a half‐life of ∼10 sec. Tip LBD1 binding did not cause gross structural changes in Lck SH3 but globally stabilized the domain and reduced the rate of partial unfolding by a factor of five. The region of partial unfolding in Lck SH3 was found to be similar to that identified for other SH3 domains that partially unfold. Although the sequence conservation between Lck SH3 and other closely related SH3 domains is high, the dynamics do not appear to be conserved.