首页> 外文期刊>Journal of Molecular Biology >The asymmetric trimeric architecture of (2Fe-2S) IscU: implications for its scaffolding during iron-sulfur cluster biosynthesis.
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The asymmetric trimeric architecture of (2Fe-2S) IscU: implications for its scaffolding during iron-sulfur cluster biosynthesis.

机译:(2Fe-2S)IscU的不对称三聚体结构:在铁硫簇生物合成过程中对其支架的影响。

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IscU is a key component of the ISC machinery and is involved in the biogenesis of iron-sulfur (Fe-S) proteins. IscU serves as a scaffold for assembly of a nascent Fe-S cluster prior to its delivery to an apo protein. Here, we report the first crystal structure of IscU with a bound [2Fe-2S] cluster from the hyperthermophilic bacterium Aquifex aeolicus, determined at a resolution of 2.3 A, using multiwavelength anomalous diffraction of the cluster. The holo IscU formed a novel asymmetric trimer that harbored only one [2Fe-2S] cluster. One iron atom of the cluster was coordinated by the S(gamma) atom of Cys36 and the N(epsilon) atom of His106, and the other was coordinated by the S(gamma) atoms of Cys63 and Cys107 on the surface of just one of the protomers. However, the cluster was buried inside the trimer between the neighboring protomers. The three protomers were conformationally distinct from one another and associated around a noncrystallographic pseudo-3-fold axis. The three flexible loop regions carrying the ligand-binding residues (Cys36, Cys63, His106 and Cys107) and the N-terminal alpha1 helices were positioned at the interfaces and underwent substantial conformational rearrangement, which stabilized the association of the asymmetric trimer. This unique trimeric A. aeolicus holo-IscU architecture was clearly distinct from other known monomeric apo-IscU/SufU structures, indicating that asymmetric trimer organization, as well as its association/dissociation, would be involved in the scaffolding function of IscU.
机译:IscU是ISC机制的关键组成部分,并参与铁硫(Fe-S)蛋白的生物发生。 IscU可作为新生Fe-S团簇的支架,然后将其递送给载脂蛋白。在这里,我们报道了使用超波长嗜热细菌Aquifex aeolicus结合的[2Fe-2S]簇的Isc的第一个晶体结构,该簇的分辨率为2.3 A,使用该簇的多波长异常衍射。完整的IscU形成了一个新颖的不对称三聚体,其中仅包含一个[2Fe-2S]簇。团簇中的一个铁原子由Cys36的S(γ)原子和His106的N(ε)原子配位,另一个由Cys63和Cys107的S(γ)原子配位。发起者。但是,簇被埋在相邻protomer之间的三聚体内部。这三个启动子在构象上彼此不同,并围绕一个非晶体伪三折轴相关。携带配体结合残基的三个柔性环区域(Cys36,Cys63,His106和Cys107)和N端alpha1螺旋位于界面处,并进行了基本构象重排,从而稳定了不对称三聚体的缔合。这种独特的三聚体aeolocus aloolicus整体IscU结构与其他已知的单体apo-IscU / SufU结构明显不同,表明不对称的三聚体组织及其缔合/解离将参与IscU的骨架功能。

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