Structural conservation of the autoinhibitory domain in SUN proteins
Structural conservation of the autoinhibitory domain in SUN proteins
复制标题
SUN 蛋白中自抑制结构域的结构保守。
DOI：
10.1016/j.bbrc.2018.02.015
复制
发表时间：
2018
影响因子：
3.1
通讯作者：
Feng Wei
中科院分区：
文献类型：
--
作者：
Xu Yang;Li Wei;Ke Huimin;Feng Wei
LINC复合体跨越核膜，由SUN和KASH蛋白组装而成。SUN1和SUN2是哺乳动物中含量最丰富的两种太阳蛋白。在SUN2中，预测的在SUN结构域之前的螺旋线圈结构域形成一个三螺旋束，构成一个自动抑制结构域(AID)来锁定SUN结构域。在这里，我们发现SUN1在SUN结构域之前也含有一个AID，并解决了SUN1的AID-SUN串联的结构。SUN1 AID还采用与SUN结构域相互作用的三螺旋束构象，并使其处于自抑制状态。AID-SUN串联中相互作用界面的中断恢复了SUN结构域与Kash肽结合的活性。结构比较进一步表明，SUN1和SUN2的AID-SUN分子的自抑制构象相似，由于相互作用界面残基的微小变化，SUN1的分子内结构域堆积略高于SUN2。因此，AID是SUN蛋白中一个保守的功能结构域，这一工作为AID介导的SUN蛋白自身抑制的对话提供了结构证据。
LINC complexes span across the nuclear envelope and are assembled by SUN and KASH proteins. SUN1 and SUN2 are the two most abundant SUN proteins in mammals. In SUN2, the predicted coiled-coil domain preceding the SUN domain forms a three-helix bundle that constitutes an autoinhibitory domain (AID) to lock down the SUN domain. Here, we found that SUN1 also contains an AID preceding the SUN domain and solved the structure of the AID-SUN tandem of SUN1. SUN1 AID also adopts a three-helix bundle conformation that interacts with the SUN domain and keeps it in an autoinhibited state. Disruptions of the interaction interface in the AID-SUN tandem restored the SUN domain activity for binding to the KASH peptide. Structural comparison further demonstrated that the autoinhibited conformations of the AID-SUN tandems from SUN1 and SUN2 are similar and the intramolecular interdomain packing in SUN1 is slightly more compact than that in SUN2 due to minor variations of the residues in the interaction interface. Thus, AID is a conserved functional domain in SUN proteins and this work provides the structural evidence to support the conversation of the AID-mediated autoinhibition of SUN proteins.