Molecular dynamics simulations in explicit water were carried out for two stacks, each composed of six 10-strand antiparallel β-sheets for two peptides corresponding to the diverging turn of two homologous Abl-SH3 domains. The first system, referred to as 10×6×MK contained the DLSFMKGE sequence from the Drosophila, while the second one, referred to as 10×6×KK, contained the human DLSFKKGE sequence. It was found that the 10×6×MK β-sheet stack is stable, but the 10×6×KK β-sheet stack is not. The stability of the 10×6×MK β-sheet stack results from the hydrophobic interactions of the methionine and phenylalanine residues and the leucine residues of the neighboring sheets. The Met, Phe, and Leu hydrophobic units make a hydrophobic core for the stack of β-sheets. During the MD run, the Met, Phe, and Leu residues of the neighboring β-sheets acted as a conformational switch moving the β-sheets so that the Phe residue interacted with the Met residue from the neighboring β-sheet. Replacement of Met by Lys destroys the hydrophobic core, which is the stability factor of the β-sheet stack. For the 10×6×KK system, individual β-sheets were preserved during simulations, but the interactions between the β-sheets were lost. The calculations of a six β-sheet stack confirm the conclusion drawn from our earlier studies of single β-sheet systems that the β-sheets must form stacks to be stabilized. These results suggest that the two conserved basic residues at the diverging turn of SH3 domains could act as gatekeepers to avoid aggregation.

译文

:在显式水中对两个堆叠进行分子动力学模拟,每个堆叠由六个肽的十链反平行β-折叠组成,对应于两个同源Abl-SH3结构域的发散转向的两个肽。第一个系统称为10×6×MK,包含来自果蝇的DLSFMKGE序列,而第二个系统称为10×6×KK,包含人的DLSFKKGE序列。发现10×6×MKβ-折叠堆叠是稳定的,但是10×6×KKβ-折叠堆叠不是稳定的。 10×6×MKβ-折叠叠层的稳定性是由蛋氨酸和苯丙氨酸残基与相邻薄片的亮氨酸残基之间的疏水性相互作用造成的。 Met,Phe和Leu疏水单元构成β-折叠堆叠的疏水核心。在MD运行期间,相邻β-折叠的Met,Phe和Leu残基充当构象开关,移动β-折叠,使Phe残基与来自相邻β-折叠的Met残基相互作用。 Lys取代Met会破坏疏水核,这是β-折叠堆叠的稳定性因素。对于10×6×KK系统,在模拟过程中保留了单独的β-折叠,但丢失了β-折叠之间的相互作用。六个β-折叠电池堆的计算证实了我们先前对单个β-折叠系统的研究得出的结论,即β-折叠必须形成要稳定的电池堆。这些结果表明,在SH3结构域的不同转弯处的两个保守的碱性残基可以充当看门人以避免聚集。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录