Dynamic interaction network involving the conserved intrinsically disordered regions in human eIF5.
Dynamic interaction network involving the conserved intrinsically disordered regions in human eIF5.
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DOI：
10.1016/j.bpc.2021.106740
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发表时间：
2022-03
影响因子：
3.8
通讯作者：
Marintchev A
中科院分区：
文献类型：
--
作者：
Paul EE;Lin KY;Gamble N;Tsai AW;Swan SHK;Yang Y;Doran M;Marintchev A
真核生物的翻译起始需要多种真核翻译起始因子，并涉及核糖体起始前复合体(PIC)的持续重构。GTPase eIF2将启动子Met-tRNAi带到PIC。在eIF5促进的起始密码子选择和GTP水解过程中，eIF2-GDP与eIF5形成复合体释放。在这里，我们报道了eIF5中的两个固有无序区(IDR)，DWEAR基序和C-末端尾(CTT)动态地接触折叠的C-末端结构域(CTD)并相互竞争。EIF5-CTD·CTT相互作用有利于eIF2β与eIF5-CTD的结合，而eIF5-CTD·DWEAR相互作用有利于eIF1a结合，这表明分子内接触重排可能在PIC重塑中发挥作用。我们发现，被CK2磷酸化的eIF5可以刺激翻译和细胞增殖，显著增加eIF5对eIF2的亲和力。我们的结果还表明，eif2β亚基至少有两个，可能有三个eif5结合位点。
Translation initiation in eukaryotes requires multiple eukaryotic translation initiation factors (eIFs) and involves continuous remodeling of the ribosomal preinitiation complex (PIC). The GTPase eIF2 brings the initiator Met-tRNAi to the PIC. Upon start codon selection and GTP hydrolysis, promoted by eIF5, eIF2-GDP is released in complex with eIF5. Here, we report that two intrinsically disordered regions (IDRs) in eIF5, the DWEAR motif and the C-terminal tail (CTT) dynamically contact the folded C-terminal domain (CTD) and compete with each other. The eIF5-CTD•CTT interaction favors eIF2β binding to eIF5-CTD, whereas the eIF5-CTD•DWEAR interaction favors eIF1A binding, which suggests how intramolecular contact rearrangement could play a role in PIC remodeling. We show that eIF5 phosphorylation by CK2, which is known to stimulate translation and cell proliferation, significantly increases the eIF5 affinity for eIF2. Our results also indicate that the eIF2β subunit has at least two, and likely three eIF5-binding sites.
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EIF5或其蛋白质模拟5MP的过表达EIF2函数，并通过延迟重新定位诱导ATF4翻译。
影响因子：
14.9
作者：
Kozel C;Thompson B;Hustak S;Moore C;Nakashima A;Singh CR;Reid M;Cox C;Papadopoulos E;Luna RE;Anderson A;Tagami H;Hiraishi H;Slone EA;Yoshino KI;Asano M;Gillaspie S;Nietfeld J;Perchellet JP;Rothenburg S;Masai H;Wagner G;Beeser A;Kikkawa U;Fleming SD;Asano K
通讯作者：
Asano K
影响因子：
14.9
作者：
Eliseev B;Yeramala L;Leitner A;Karuppasamy M;Raimondeau E;Huard K;Alkalaeva E;Aebersold R;Schaffitzel C
通讯作者：
Schaffitzel C
影响因子：
14.9
作者：
Jennings MD;Kershaw CJ;White C;Hoyle D;Richardson JP;Costello JL;Donaldson IJ;Zhou Y;Pavitt GD
通讯作者：
Pavitt GD
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
10.5
作者：
Pisarev, AV;Kolupaeva, VG;Pestova, TV
通讯作者：
Pestova, TV