Intra- and inter-molecular regulation by intrinsically-disordered regions governs PUF protein RNA binding.
Intra- and inter-molecular regulation by intrinsically-disordered regions governs PUF protein RNA binding.
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DOI：
10.1038/s41467-023-43098-1
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发表时间：
2023-11-13
影响因子：
16.6
通讯作者：
Hall, Traci M. Tanaka
中科院分区：
文献类型：
--
作者：
Qiu, Chen;Zhang, Zihan;Wine, Robert N.;Campbell, Zachary T.;Zhang, Jun;Hall, Traci M. Tanaka
PUF蛋白的特征在于球状RNA结合结构域。它们还与调节其RNA结合活性的伴侣蛋白相互作用。秀丽隐杆线虫PUF蛋白fem-3结合因子-2（FBF-2）与内在无序的侧向信号传导靶标-1（LST-1）合作，以调节生殖系干细胞中的靶标mRNA。在这里，我们报告说，一个内在的无序区域（IDR）在C-末端的FBF-2的自抑制其RNA结合的亲和力，通过增加关闭率的RNA结合。此外，FBF-2的C-末端区域与其球状RNA结合结构域在LST-1结合的相同位点相互作用。这种分子内相互作用抑制了结合的RNA的5′端附近的负电性氨基酸残基簇以抑制RNA结合。因此，LST-1结合FBF-2 C-末端的位置释放了自身抑制并增加了RNA结合亲和力。这种由IDR驱动的调节机制为FBF-2和LST-1在生殖系干细胞自我更新中的相互依赖性提供了生物化学和生物物理学解释。FBF-2和LST-1抑制gld-1 mRNA表达，维持C.线虫生殖系干细胞作者表明，FBF-2的内在无序区域会自动抑制其RNA结合。LST-1拮抗这种相互作用以促进RNA结合。
PUF proteins are characterized by globular RNA-binding domains. They also interact with partner proteins that modulate their RNA-binding activities. Caenorhabditis elegans PUF protein fem-3 binding factor-2 (FBF-2) partners with intrinsically disordered Lateral Signaling Target-1 (LST-1) to regulate target mRNAs in germline stem cells. Here, we report that an intrinsically disordered region (IDR) at the C-terminus of FBF-2 autoinhibits its RNA-binding affinity by increasing the off rate for RNA binding. Moreover, the FBF-2 C-terminal region interacts with its globular RNA-binding domain at the same site where LST-1 binds. This intramolecular interaction restrains an electronegative cluster of amino acid residues near the 5′ end of the bound RNA to inhibit RNA binding. LST-1 binding in place of the FBF-2 C-terminus therefore releases autoinhibition and increases RNA-binding affinity. This regulatory mechanism, driven by IDRs, provides a biochemical and biophysical explanation for the interdependence of FBF-2 and LST-1 in germline stem cell self-renewal. FBF-2 and LST-1 repress gld-1 mRNA expression to maintain C. elegans germline stem cells. The authors show that an intrinsically-disordered region of FBF-2 autoinhibits its RNA binding. LST-1 antagonizes this interaction to promote RNA binding.
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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：
7.7
作者：
Bhat, Vandita D.;McCann, Kathleen L.;Campbell, Zachary T.
通讯作者：
Campbell, Zachary T.
影响因子：
4.6
作者：
Haupt, Kimberly A.;Enright, Amy L.;Kimble, Judith
通讯作者：
Kimble, Judith
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
64.5
作者：
Edwards, TA;Pyle, SE;Aggarwal, AK
通讯作者：
Aggarwal, AK