Inhibition of FAM46/TENT5 activity by BCCIPα adopting a unique fold.
Inhibition of FAM46/TENT5 activity by BCCIPα adopting a unique fold.
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通过BCCIPα抑制FAM46/TENT5活性，采用独特的折叠。
DOI：
10.1126/sciadv.adf5583
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发表时间：
2023-04-05
期刊：
影响因子：
13.6
通讯作者：
Zhang, Xuewu
中科院分区：
文献类型：
--
作者：
Liu, Shun;Chen, Hua;Yin, Yan;Lu, Defen;Gao, Guoming;Li, Jie;Bai, Xiao-Chen;Zhang, Xuewu
FAM46(也称为TENT5)蛋白是一种非规范的多(A)聚合酶(PAPs)，参与调节RNA的稳定性。对FAM46的调控机制知之甚少。在这里，我们报告了核蛋白BCCIPα，而不是选择性剪接的异构体BCCIPβ，结合FAM46并抑制其PAP活性。出人意料的是，我们的FAM46A/BCCIPα和FAM46C/BCCIPα复合体的结构表明，尽管BCCIPα具有大部分序列相同，仅在C-末端存在差异，但它采用了与BCCIPβ完全不同的独特结构。中银国际α独特的C末端片段支持采用独特的折叠，但不直接与FAM46相互作用。βα和FAM46中的β薄片并排包装，形成加长的FAM46薄片。α的一个螺旋-环-螺旋片段插入到FAM46的活性部位间隙，从而抑制了PAP的活性。我们的结果表明，BCCIPα的独特折叠是其与FAM46相互作用和功能调控的基础。BCCIPɑ采用与其近亲BCCIPβ完全不同的结构，抑制FAM46蛋白的活性。
The FAM46 (also known as TENT5) proteins are noncanonical poly(A) polymerases (PAPs) implicated in regulating RNA stability. The regulatory mechanisms of FAM46 are poorly understood. Here, we report that the nuclear protein BCCIPα, but not the alternatively spliced isoform BCCIPβ, binds FAM46 and inhibits their PAP activity. Unexpectedly, our structures of the FAM46A/BCCIPα and FAM46C/BCCIPα complexes show that, despite sharing most of the sequence and differing only at the C-terminal portion, BCCIPα adopts a unique structure completely different from BCCIPβ. The distinct C-terminal segment of BCCIPα supports the adoption of the unique fold but does not directly interact with FAM46. The β sheets in BCCIPα and FAM46 pack side by side to form an extended β sheet. A helix-loop-helix segment in BCCIPα inserts into the active site cleft of FAM46, thereby inhibiting the PAP activity. Our results together show that the unique fold of BCCIPα underlies its interaction with and functional regulation of FAM46. BCCIPɑ, adopting a completely different structure from its close relative BCCIPβ, inhibits the activity of the FAM46 proteins.
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影响因子：
3.7
作者：
Etokebe GE;Zienolddiny S;Kupanovac Z;Enersen M;Balen S;Flego V;Bulat-Kardum L;Radojčić-Badovinac A;Skaug V;Bakke P;Haugen A;Dembic Z
通讯作者：
Dembic Z
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：
3.5
作者：
Kelemen O;Convertini P;Zhang Z;Wen Y;Shen M;Falaleeva M;Stamm S
通讯作者：
Stamm S
影响因子：
11.2
作者：
Huang YY;Dai L;Gaines D;Droz-Rosario R;Lu H;Liu J;Shen Z
通讯作者：
Shen Z
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH