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DOI | 10.1038/s41467-018-03861-1 |
An allosteric conduit facilitates dynamic multisite substrate recognition by the SCFCdc4 ubiquitin ligase | |
Csizmok, Veronika1; Orlicky, Stephen2; Cheng, Jing3; Song, Jianhui4,5,6; Bah, Alaji1; Delgoshaie, Neda3; Lin, Hong1; Mittag, Tanja1,7; Sicheri, Frank2,4,5; Chan, Hue Sun4,5; Tyers, Mike2,3,8; Forman-Kay, Julie D.1,4 | |
2017-01-03 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | Canada; Peoples R China; USA; Switzerland |
英文摘要 | The ubiquitin ligase SCFCdc4 mediates phosphorylation-dependent elimination of numerous substrates by binding one or more Cdc4 phosphodegrons (CPDs). Methyl-based NMR analysis of the Cdc4 WD40 domain demonstrates that Cyclin E, Sic1 and Ash1 degrons have variable effects on the primary Cdc4(WD40) binding pocket. Unexpectedly, a Sic1-derived multi-CPD substrate (pSic1)perturbs methyls around a previously documented allosteric binding site for the chemical inhibitor SCF-I2. NMR cross-saturation experiments confirm direct contact between pSic1 and the allosteric pocket. Phosphopeptide affinity measurements reveal negative allosteric communication between the primary CPD and allosteric pockets. Mathematical modelling indicates that the allosteric pocket may enhance ultra-sensitivity by tethering pSic1 to Cdc4. These results suggest negative allosteric interaction between two distinct binding pockets on the Cdc4(WD40) domain may facilitate dynamic exchange of multiple CPD sites to confer ultrasensitive dependence on substrate phosphorylation. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000391020500001 |
WOS关键词 | S-PHASE ; PHOSPHORYLATION SITES ; POLYVALENT LIGAND ; PROTEIN COMPLEXES ; STRUCTURAL BASIS ; TROSY NMR ; SIC1 ; DEGRADATION ; INHIBITOR ; AFFINITY |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203774 |
专题 | 资源环境科学 |
作者单位 | 1.Hosp Sick Children, Mol Struct & Funct, Toronto, ON M5G 0A4, Canada; 2.Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada; 3.Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada; 4.Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada; 5.Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada; 6.Qingdao Univ Sci & Technol, Sch Polymer Sci & Engn, Qingdao 266042, Shandong, Peoples R China; 7.St Jude Childrens Res Hosp, Dept Biol Struct, 332 N Lauderdale St, Memphis, TN 38105 USA; 8.Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland |
推荐引用方式 GB/T 7714 | Csizmok, Veronika,Orlicky, Stephen,Cheng, Jing,et al. An allosteric conduit facilitates dynamic multisite substrate recognition by the SCFCdc4 ubiquitin ligase[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Csizmok, Veronika.,Orlicky, Stephen.,Cheng, Jing.,Song, Jianhui.,Bah, Alaji.,...&Forman-Kay, Julie D..(2017).An allosteric conduit facilitates dynamic multisite substrate recognition by the SCFCdc4 ubiquitin ligase.NATURE COMMUNICATIONS,8. |
MLA | Csizmok, Veronika,et al."An allosteric conduit facilitates dynamic multisite substrate recognition by the SCFCdc4 ubiquitin ligase".NATURE COMMUNICATIONS 8(2017). |
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