Structure of a trimeric nucleoporin complex reveals alternate oligomerization states
Structure of a trimeric nucleoporin complex reveals alternate oligomerization states
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DOI：
10.1073/pnas.0909373106
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发表时间：
2009-10-20
影响因子：
11.1
通讯作者：
Hoelz, Andre
中科院分区：
文献类型：
--
作者：
Nagy, Vivien;Hsia, Kuo-Chiang;Hoelz, Andre
七聚体Nup84复合物构成了核孔复合物的进化上保守的构件。在这里，我们提出了异源三聚体Sec13.Nup145C.Nup84复合物的晶体结构，七聚体的中心，在3.2埃的分辨率。Nup84形成U形α螺旋螺线管结构域，拓扑学上类似于七聚体的另外两个成员Nup145C和Nup85。Nup84和Nup145C之间的相互作用是通过位于两个Nup84环的扭结区域中的疏水界面介导的，所述疏水界面通过两个长Nup84环的额外相互作用而增强。Nup84结合位点与Nup145C的同源二聚化界面部分重叠，表明竞争结合事件。将伸长的Z形异源三聚体拟合到七聚体的电子显微镜（EM）封套中表明在Nup145C.Nup84界面处发生结构变化。将所有七聚体组分的晶体结构对接到EM包膜中构成了朝向完成Nup84复合物的结构表征的主要进展。
The heptameric Nup84 complex constitutes an evolutionarily conserved building block of the nuclear pore complex. Here, we present the crystal structure of the heterotrimeric Sec13.Nup145C.Nup84 complex, the centerpiece of the heptamer, at 3.2-angstrom resolution. Nup84 forms a U-shaped alpha-helical solenoid domain, topologically similar to two other members of the heptamer, Nup145C and Nup85. The interaction between Nup84 and Nup145C is mediated via a hydrophobic interface located in the kink regions of the two solenoids that is reinforced by additional interactions of two long Nup84 loops. The Nup84 binding site partially overlaps with the homo-dimerization interface of Nup145C, suggesting competing binding events. Fitting of the elongated Z-shaped heterotrimer into electron microscopy (EM) envelopes of the heptamer indicates that structural changes occur at the Nup145C.Nup84 interface. Docking the crystal structures of all heptamer components into the EM envelope constitutes a major advance toward the completion of the structural characterization of the Nup84 complex.