The Role of the Arginine in the Conserved N-Terminal Domain RLFDQxFG Motif of Human Small Heat Shock Proteins HspB1, HspB4, HspB5, HspB6, and HspB8.
The Role of the Arginine in the Conserved N-Terminal Domain RLFDQxFG Motif of Human Small Heat Shock Proteins HspB1, HspB4, HspB5, HspB6, and HspB8.
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DOI：
10.3390/ijms19072112
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发表时间：
2018-07-20
影响因子：
5.6
通讯作者：
Gusev NB
中科院分区：
文献类型：
--
作者：
Shatov VM;Weeks SD;Strelkov SV;Gusev NB
脊椎动物小分子热休克蛋白（small heat shock proteins，sHsp）的N端结构域保守性较差，但其核心结构域在sHsp家族的许多成员中都有保留。该RLFDQxFG基序的作用仍然难以捉摸。我们分析了这个保守的八肽序列的第一个精氨酸残基在五种人sHsps（HspB 1，HspB 4，HspB 5，HspB 6和HspB 8）中的特定作用。用丙氨酸取代这种精氨酸会引起相关HspB 1和HspB 8的热稳定性和/或固有荧光的变化，但对HspB 4、HspB 5和HspB 6的相同生物物理性质仅产生适度的变化，这些性质共同属于脊椎动物sHsps的另一个进化枝。去除带正电荷的Arg侧链导致HspB 1的大寡聚体的不稳定和HspB 5的较小尺寸的寡聚体的形成。该突变仅引起HspB 4和HspB 6结构的微小变化。相反，HspB 8中的突变伴随着从二聚体向更大的寡聚体的形成的平衡的转变。我们的结论是RLFDQxFG基序在几个sHsp直系同源物的结构中起着不同的作用。这种作用与各自sHsps的进化关系相关，但最终，它反映了该基序的序列背景。
Although the N-terminal domain of vertebrate small heat shock proteins (sHsp) is poorly conserved, it contains a core motif preserved in many members of the sHsp family. The role of this RLFDQxFG motif remains elusive. We analyzed the specific role of the first arginine residue of this conserved octet sequence in five human sHsps (HspB1, HspB4, HspB5, HspB6, and HspB8). Substitution of this arginine with an alanine induced changes in thermal stability and/or intrinsic fluorescence of the related HspB1 and HspB8, but yielded only modest changes in the same biophysical properties of HspB4, HspB5, and HspB6 which together belong to another clade of vertebrate sHsps. Removal of the positively charged Arg side chain resulted in destabilization of the large oligomers of HspB1 and formation of smaller size oligomers of HspB5. The mutation induced only minor changes in the structure of HspB4 and HspB6. In contrast, the mutation in HspB8 was accompanied by shifting the equilibrium from dimers towards the formation of larger oligomers. We conclude that the RLFDQxFG motif plays distinct roles in the structure of several sHsp orthologs. This role correlates with the evolutionary relationship of the respective sHsps, but ultimately, it reflects the sequence context of this motif.
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影响因子：
3.7
作者：
Heirbaut M;Beelen S;Strelkov SV;Weeks SD
通讯作者：
Weeks SD
影响因子：
4.8
作者：
Heirbaut, Michelle;Lermyte, Frederik;Weeks, Stephen D.
通讯作者：
Weeks, Stephen D.
影响因子：
5.7
作者：
Hanazono, Yuya;Takeda, Kazuki;Miki, Kunio
通讯作者：
Miki, Kunio
影响因子：
--
作者：
Alshammari, Eyad M. A.;Khan, Saif;Haque, Shafiul
通讯作者：
Haque, Shafiul
DOI：
10.1016/j.bbrc.2004.01.130
发表时间：
2004-03-19
影响因子：
3.1
作者：
Kim, MV;Seit-Nebi, AS;Gusev, NB
通讯作者：
Gusev, NB