Structure of the pre-mRNA leakage 39-kDa protein reveals a single domain of integrated zf-C3HC and Rsm1 modules.
Structure of the pre-mRNA leakage 39-kDa protein reveals a single domain of integrated zf-C3HC and Rsm1 modules.
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DOI：
10.1038/s41598-022-22183-3
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发表时间：
2022-10-21
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
据报道，在酿酒酵母中，前体mRNA泄漏39-kDa蛋白（ScPml 39）在通过核孔复合物（NPC）输出之前保留未剪接的前体mRNA。Pml 39同系物以外的真菌科目前是未知的，和机制的洞察Pml 39功能缺乏。在此，我们以2.5 μ m的分辨率确定了ScPml 39的晶体结构，以促进在粟酒裂殖酵母科之外的直系同源物的发现，例如在粟酒裂殖酵母或人类中。晶体结构揭示了整合的zf-C3 HC和Rsm 1模块，它们通过疏水界面紧密结合形成单个结构域。zf-C3 HC和Rsm 1模块都属于含锌的BIR（杆状病毒IAP重复）样超家族，经典BIR结构域的关键残基是保守的。Pml 39模块的独特特征是指Zn配位残基之间的间隔，在zf-C3 HC和Rsm 1模块中产生基本倾斜的螺旋αC，在Rsm 1模块中产生额外的螺旋αAB′。保守的关键残基负责其独特的功能，确定S。粟酒裂殖酵母Rsm 1和智人NIPA/ZC 3 HC 1作为ScPml 39的结构直向同源物。基于最近NIPA/ZC 3 HC 1作为稳定NPC核篮的支架蛋白的功能表征，我们的数据表明ScPml 39在S.酿酒。
In Saccharomyces cerevisiae, the pre-mRNA leakage 39-kDa protein (ScPml39) was reported to retain unspliced pre-mRNA prior to export through nuclear pore complexes (NPCs). Pml39 homologs outside the Saccharomycetaceae family are currently unknown, and mechanistic insight into Pml39 function is lacking. Here we determined the crystal structure of ScPml39 at 2.5 Å resolution to facilitate the discovery of orthologs beyond Saccharomycetaceae, e.g. in Schizosaccharomyces pombe or human. The crystal structure revealed integrated zf-C3HC and Rsm1 modules, which are tightly associated through a hydrophobic interface to form a single domain. Both zf-C3HC and Rsm1 modules belong to the Zn-containing BIR (Baculovirus IAP repeat)-like super family, with key residues of the canonical BIR domain being conserved. Features unique to the Pml39 modules refer to the spacing between the Zn-coordinating residues, giving rise to a substantially tilted helix αC in the zf-C3HC and Rsm1 modules, and an extra helix αAB′ in the Rsm1 module. Conservation of key residues responsible for its distinct features identifies S. pombe Rsm1 and Homo sapiens NIPA/ZC3HC1 as structural orthologs of ScPml39. Based on the recent functional characterization of NIPA/ZC3HC1 as a scaffold protein that stabilizes the nuclear basket of the NPC, our data suggest an analogous function of ScPml39 in S. cerevisiae.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
影响因子：
4.8
作者：
Bourhis, Eric;Hymowitz, Sarah G.;Cochran, Andrea G.
通讯作者：
Cochran, Andrea G.
ZC3HC1是核篮的新型固有组成部分，居住在与TPR的相互依赖状态下。
影响因子：
6
作者：
Gunkel P;Iino H;Krull S;Cordes VC
通讯作者：
Cordes VC
影响因子：
5.7
作者：
Brockmann, Christoph;Soucek, Sharon;Kuhlmann, Sonja I.;Mills-Lujan, Katherine;Kelly, Seth M.;Yang, Ji-Chun;Iglesias, Nahid;Stutz, Francoise;Corbett, Anita H.;Neuhaus, David;Stewart, Murray
通讯作者：
Stewart, Murray