Partial unfolding of diverse SH3 domains on a wide timescale
Partial unfolding of diverse SH3 domains on a wide timescale
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DOI：
10.1016/j.jmb.2006.01.075
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发表时间：
2006-04-14
影响因子：
5.6
通讯作者：
Engen, JR
中科院分区：
文献类型：
--
作者：
Wales, TE;Engen, JR
SH3结构域是在许多蛋白质中发现的小的模块化结构域，特别是信号转导蛋白如酪氨酸激酶。虽然对SH3结构域的序列和三级结构了解很多，但对其溶液动力学知之甚少。先前使用氢交换（HX）质谱法（MS）在Hck SH3结构域中鉴定了在生理条件下发生的缓慢的部分解折叠事件。为了确定这种解折叠是否是Hck SH3所特有的，使用HX MS分析了11个其他SH3结构域：7个来自Src家族激酶的SH3结构域和5个来自各种蛋白质的SH3结构域。发现了各种各样的解折叠速率，解折叠半衰期范围从Is到Ih。林恩和α-血影蛋白SH 3结构域在β链D和E以及部分RT环中表现出缓慢的部分解折叠。Hck SH3在同一区域也经历了部分解折叠，这意味着在该区域的结构域中的独特特征是部分解折叠的原因。然而，部分解折叠不是序列保守的函数。虽然Fyn和Yes SH3结构域在序列上与Hck SH3非常相似，但它们没有表现出部分解折叠的证据。总体而言，结果表明，虽然SH3结构域的三级结构是高度保守的，但SH3结构域的动力学是可变的。(c)2006爱思唯尔有限公司保留所有权利。
SH3 domains are small, modular domains that are found in many proteins, especially signal transduction proteins such as tyrosine kinases. While much is known about the sequences and tertiary structures of SH3 domains, far less is known about their solution dynamics. A slow, partial unfolding event that occurs under physiological conditions was previously identified in the Hck SH3 domain using hydrogen exchange (HX) mass spectrometry (MS). To determine if this unfolding was unique to Hck SH3, HX MS was used to analyze 11 other SH3 domains: seven SH3 domains from Src-family kinases and five SH3 domains from various proteins. A wide variety of unfolding rates were found, with unfolding half-lives ranging from I s to I h. The Lyn and alpha-spectrin SH3 domains exhibited slow, partial unfolding in beta strands D and E and part of the RT-loop. Hck SH3 also underwent partial unfolding in the same region, implying that a unique feature in this area of the domains is responsible for the partial unfolding. Partial unfolding was, however, not a function of sequence conservation. Although the Fyn and Yes SH3 domains are very similar to Hck SH3 in sequence, they exhibited no evidence of partial unfolding. Overall, the results suggest that while the tertiary structure of SH3 domains is highly conserved, the dynamics of SH3 domains are variable. (c) 2006 Elsevier Ltd. All rights reserved.